The Role of ‘Forever Chemicals’ in Cancer Metastasis

Transcript

00:00 --> 00:03Funding for Yale Cancer Answers is
00:03 --> 00:06provided by Smilow Cancer Hospital.
00:06 --> 00:08Welcome to Yale Cancer Answers
00:08 --> 00:10with Doctor Anees Chagpar.
00:10 --> 00:11Yale Cancer Answers features the
00:11 --> 00:13latest information on cancer care
00:13 --> 00:15by welcoming oncologists and
00:15 --> 00:17specialists who are on the forefront
00:17 --> 00:19of the battle to fight cancer.
00:19 --> 00:21This week it's a conversation about
00:21 --> 00:24the role of forever chemicals in cancer
00:24 --> 00:26metastasis with Doctor Caroline Johnson.
00:26 --> 00:28Doctor Johnson is an associate
00:28 --> 00:30professor of epidemiology and
00:30 --> 00:31Environmental Health Sciences at
00:31 --> 00:33the Yale School of Public Health,
00:33 --> 00:35and Doctor Chagpar is a professor
00:35 --> 00:36of surgical oncology at the
00:36 --> 00:38Yale School of Medicine.
00:38 --> 00:40Caroline, maybe we can start off by
00:40 --> 00:42you telling us a little bit more
00:42 --> 00:44about yourself and what it is you do.
00:44 --> 00:46For the past seven or eight years
00:46 --> 00:49my main research interests have been to
00:49 --> 00:51understand the metabolism of colorectal
00:51 --> 00:53cancer and actually how this can
00:53 --> 00:56relate to the prognosis of the patient.
00:56 --> 00:57And one of the ways that we do this
00:57 --> 01:00is actually by looking at those small
01:00 --> 01:01differences between individuals
01:01 --> 01:03that can actually influence their
01:03 --> 01:05metabolism and their prognosis.
01:05 --> 01:08So aspects such as the genetics of the
01:08 --> 01:10tumour or an exposure that they may
01:10 --> 01:13receive or even things like where the
01:13 --> 01:15tumour occurs within the colorectum
01:15 --> 01:17or even the sex of the individual.
01:17 --> 01:19As we know this can also affect
01:19 --> 01:21the prognosis of the patient.
01:22 --> 01:26And so we can kind of
01:26 --> 01:28understand that individuals may
01:28 --> 01:30have different prognosis either
01:30 --> 01:34based on genetics of the tumor or
01:34 --> 01:36their environmental factors,
01:36 --> 01:39their gender, etcetera.
01:39 --> 01:41Talk a little bit more about
01:41 --> 01:43how that translates into this
01:43 --> 01:45metabolism of the cancer?
01:45 --> 01:47Many of us, when we think about metabolism,
01:47 --> 01:50we're thinking about our own metabolism,
01:50 --> 01:53calories in, calories out, weight loss,
01:53 --> 01:55weight gain, that kind of thing.
01:55 --> 01:59Clearly tumors also have a metabolism in
01:59 --> 02:03terms of how they grow and spread.
02:03 --> 02:07Talk a little bit more about how those
02:07 --> 02:11factors influence that metabolism.
02:11 --> 02:13Yeah, that's a really good point actually.
02:13 --> 02:17So when we talk about tumor metabolism,
02:17 --> 02:19we're talking about specifically what
02:19 --> 02:21is happening in those groups of cells
02:21 --> 02:24that are growing within the the tumor.
02:24 --> 02:26And as the the tumor starts to grow,
02:26 --> 02:28it's actually very metabolically
02:28 --> 02:32dependent for its ability to metastasize.
02:32 --> 02:34So when the the primary tumor,
02:34 --> 02:37so the initial tumor in the case of
02:37 --> 02:39colorectal cancer is present in the
02:39 --> 02:42colon or the rectum it actually starts
02:42 --> 02:45to produce some small chemicals called
02:45 --> 02:47metabolites that can be quite acidic.
02:47 --> 02:50So this can increase the local
02:50 --> 02:52environment of the tumor,
02:52 --> 02:55increase its acidity by
02:55 --> 02:57decreasing the pH and this can
02:57 --> 02:58actually cause breakdown of the
02:58 --> 03:01membranes in the tumor and
03:01 --> 03:03the cell membranes and cause the
03:03 --> 03:04cells to undergo intraversation so
03:04 --> 03:07they can then do things like move
03:07 --> 03:09towards a circulatory system.
03:09 --> 03:10So that's very dependent on
03:10 --> 03:12the metabolism of the tumor.
03:12 --> 03:14And then again when they enter
03:14 --> 03:16the circulatory system the
03:16 --> 03:17individual tumor cells,
03:17 --> 03:19they're bombarded with things
03:19 --> 03:20like oxidative stress.
03:21 --> 03:23So the metabolism of the tumor
03:23 --> 03:26cells themselves change again to
03:26 --> 03:29counteract this oxidative stress.
03:29 --> 03:30And then when these tumor cells
03:30 --> 03:32reach a new organ or a new site
03:32 --> 03:34such as the lung or the liver in
03:34 --> 03:36the case of colorectal cancer,
03:36 --> 03:39they undergo this state of dormancy.
03:39 --> 03:41And then they ramp up their metabolism
03:41 --> 03:43again by taking in different
03:43 --> 03:45nutrients from those new sites,
03:45 --> 03:46so from the surrounding tissue
03:46 --> 03:48in the lung or the liver.
03:48 --> 03:51And then they start to produce
03:51 --> 03:53things like nucleic acids and
03:53 --> 03:55amino acids and proteins to survive
03:55 --> 03:58and grow in that new site.
03:58 --> 04:01So actually metabolism is really
04:01 --> 04:03intrinsic to going from being
04:03 --> 04:05in that initial primary tumor
04:05 --> 04:08state to the metastatic state.
04:10 --> 04:13And so that really interesting when
04:13 --> 04:16we think about how these cancer cells kind
04:16 --> 04:19of use different milieu that they may find
04:19 --> 04:22themselves in to really take advantage
04:22 --> 04:25of the system to grow and flourish.
04:25 --> 04:27You know as you think about that,
04:27 --> 04:29some of our listeners may be thinking
04:29 --> 04:31about how do you counteract that.
04:32 --> 04:36And I think some of this then
04:36 --> 04:39leads to people having perceptions
04:39 --> 04:42that may or may not be true.
04:42 --> 04:44So for example,
04:44 --> 04:46when we think about cancer cells,
04:46 --> 04:51as you mentioned, initially creating a
04:51 --> 04:54acidic environment where they can then
04:54 --> 04:57migrate towards the circulatory system,
04:57 --> 04:58some people might think,
04:58 --> 05:01well then that's a good reason to try to,
05:01 --> 05:02for example,
05:02 --> 05:06drink alkaline water or try to
05:06 --> 05:09alkalinize your system so that cancer
05:09 --> 05:12cells then don't grow and spread.
05:12 --> 05:15Is there any fact to that?
05:15 --> 05:17Is there any weight to that
05:17 --> 05:18kind of an argument?
05:19 --> 05:20Yeah, that is a really good point.
05:20 --> 05:23And in this case,
05:23 --> 05:26I don't think that would work.
05:26 --> 05:28I think because
05:28 --> 05:30there's many different aspects as
05:30 --> 05:32well that can control the local
05:32 --> 05:34environment within the tumor.
05:34 --> 05:35So some of these
05:35 --> 05:37are due to the genetic make up
05:37 --> 05:39of the tumor that
05:39 --> 05:41can control the expression of
05:41 --> 05:44proteins that control how these
05:44 --> 05:46metabolites are actually produced.
05:46 --> 05:48And there's other aspects as well,
05:49 --> 05:51such as the presence of the microbiome,
05:52 --> 05:53which we know that there are thousands
05:53 --> 05:54of different species.
05:54 --> 05:57They all have their own genome and
05:57 --> 05:59they can produce and metabolise
05:59 --> 06:01various metabolites as well and
06:01 --> 06:03control this local environment.
06:03 --> 06:07So it really is a complicated
06:07 --> 06:10mix of various factors that
06:10 --> 06:12can influence the metabolism
06:12 --> 06:15within the colorectum itself
06:15 --> 06:17and things that you may ingest
06:17 --> 06:19obviously go through various processes
06:19 --> 06:21in your body to actually
06:21 --> 06:24reach that area of the colon.
06:25 --> 06:27So direct ingestion of something
06:27 --> 06:29like alkaline water I wouldn't
06:29 --> 06:30expect would
06:30 --> 06:31affect an acidic environment,
06:31 --> 06:34within the the tumor itself.
06:35 --> 06:40So let's dive a bit more into your research
06:40 --> 06:43that hopefully will be more impactful.
06:43 --> 06:46Talk a little bit more about how
06:46 --> 06:48your study of this metabolism,
06:48 --> 06:50what exactly you're doing in your
06:50 --> 06:53lab and how you hope that
06:53 --> 06:55that will then lead to meaningful
06:55 --> 06:57impacts for patients long term.
06:58 --> 07:00We're trying to look at
07:00 --> 07:02all these different
07:02 --> 07:06aspects of individuals such as
07:06 --> 07:07we've done a lot of research
07:07 --> 07:08so far on
07:08 --> 07:10whether the sex of the patient
07:10 --> 07:13can influence prognosis
07:13 --> 07:15and other aspects too.
07:15 --> 07:18And the way that we look at
07:18 --> 07:21this is by using a technology called
07:21 --> 07:24mass spectrometry based metabolomics.
07:24 --> 07:27And what we do here is that
07:27 --> 07:29we take the tumor samples from individuals.
07:29 --> 07:33So our very first study actually looked
07:33 --> 07:36at 200 different tumor tissues from
07:36 --> 07:39males and females and we analyze each
07:39 --> 07:42of these tumors to see what their
07:43 --> 07:44metabolism look like.
07:44 --> 07:46So all the individual metabolites
07:46 --> 07:47that were present.
07:47 --> 07:49So we take these tumor samples
07:49 --> 07:51and we use this technology called
07:51 --> 07:53liquid chromatography based
07:53 --> 07:55mass spectrometry metabolomics.
07:55 --> 07:58And this essentially is like using a giant
07:58 --> 08:00molecular sieve and a weighing scale.
08:01 --> 08:02And it can give chemical information
08:02 --> 08:05on the thousands of different small
08:05 --> 08:07molecules or chemicals or metabolites
08:07 --> 08:09that are present within each tumor.
08:09 --> 08:11And these metabolites can come
08:11 --> 08:12from things like
08:12 --> 08:14your diet, from different
08:14 --> 08:15environmental exposures.
08:15 --> 08:17If they're at a high enough level,
08:17 --> 08:19we can tell about different aspects
08:19 --> 08:21of microbial metabolism as well.
08:21 --> 08:23And we look at all of these
08:23 --> 08:25metabolites together as
08:25 --> 08:27as they do have some dependency
08:27 --> 08:30on each other and we can predict
08:30 --> 08:32what biological effects these
08:32 --> 08:34metabolites could be having.
08:34 --> 08:36And I guess one analogy that I like
08:36 --> 08:39to think about when I'm thinking
08:39 --> 08:41of metabolites and how they link
08:41 --> 08:43to biology is kind of like the
08:43 --> 08:45New York City subway system.
08:45 --> 08:48So we know that the New York City subway
08:48 --> 08:50system has various different train
08:50 --> 08:52lines and each of these train lines
08:52 --> 08:54has specific subway stations along
08:54 --> 08:56them and we know which train lines go
08:56 --> 08:58along which to which subway stations.
08:58 --> 09:00It's the same with metabolism.
09:00 --> 09:02So if we think of each of these train
09:02 --> 09:04lines as metabolic pathways and each of
09:04 --> 09:06these subway stations as metabolites,
09:06 --> 09:08we know which metabolites are linked
09:08 --> 09:10to certain metabolic pathways that
09:10 --> 09:12control metabolism and control biology.
09:12 --> 09:17So things like controlling oxidative stress,
09:17 --> 09:19producing energy,
09:19 --> 09:20controlling fat metabolism
09:20 --> 09:21and things like that.
09:21 --> 09:23So then we start to put together a
09:23 --> 09:25picture of how certain factors such
09:25 --> 09:28as the influence of an exposure
09:28 --> 09:30or the sex of the individual can
09:30 --> 09:32alter these aspects of biology and
09:32 --> 09:34can be health indicators for us.
09:36 --> 09:38And that really interesting
09:38 --> 09:41and important work in the sense that,
09:41 --> 09:43you know, if you're finding that there
09:43 --> 09:46are differences based on gender in
09:46 --> 09:48terms of these metabolites, then by
09:48 --> 09:50definition that means that the biology,
09:50 --> 09:54how men and women, their biologic systems
09:54 --> 09:58process these metabolites is different.
09:58 --> 10:01And so that has really profound implications,
10:01 --> 10:04not only in terms of the differences,
10:04 --> 10:06in terms of the rate at which
10:06 --> 10:08men and women get cancers,
10:08 --> 10:09but potentially in terms of
10:09 --> 10:11how they're treated as well.
10:11 --> 10:11Is that right?
10:12 --> 10:14Yeah, that is correct.
10:14 --> 10:15And in colorectal cancer,
10:15 --> 10:17to my knowledge, I'm not a clinician.
10:17 --> 10:21I'm a basic science researcher,
10:21 --> 10:24is that men and women aren't stratified
10:25 --> 10:26by sex for treatment.
10:26 --> 10:29And there have been a couple of
10:29 --> 10:32publications that I saw over the past year
10:32 --> 10:35where they've seen that men and women have
10:35 --> 10:37different outcomes when they receive
10:37 --> 10:39the same type of chemotherapeutics.
10:39 --> 10:41So using combination chemotherapeutics,
10:41 --> 10:44one study saw that the female
10:44 --> 10:46patients actually had a poorer
10:46 --> 10:48prognosis than the male patients.
10:48 --> 10:49And this is probably
10:49 --> 10:51a combination of
10:51 --> 10:54metabolism and immune responses.
10:54 --> 10:56So yes, there's definitely
10:56 --> 10:58a difference that we see,
10:58 --> 11:00and in terms of
11:00 --> 11:01incidence and mortality,
11:02 --> 11:04males generally have a higher incidence
11:04 --> 11:06and mortality from colorectal cancer.
11:06 --> 11:08But for women, for colorectal cancer
11:09 --> 11:11it is still the third leading cause
11:11 --> 11:13of cancer related deaths for them.
11:13 --> 11:17So it is still very important I think to
11:17 --> 11:20study both males and females separately,
11:20 --> 11:22in terms of colorectal cancer,
11:23 --> 11:26and I think
11:26 --> 11:29we've seen similar things in terms
11:29 --> 11:31of research looking at gender
11:31 --> 11:33differences even in things like heart
11:33 --> 11:35disease where initially all of the
11:35 --> 11:37trials were done using white males.
11:37 --> 11:40And what we then discovered was that
11:40 --> 11:43men and women are different in terms
11:43 --> 11:45of their cardiovascular health.
11:45 --> 11:48And that's why I think it's so important
11:48 --> 11:51that we try to get a diversity of people
11:51 --> 11:53to participate in clinical trials
11:53 --> 11:56so that we really can understand the
11:56 --> 11:58biology of different particular
11:58 --> 12:02groups who may have different biologies.
12:04 --> 12:07I think that certainly
12:07 --> 12:10might be an area for further work.
12:10 --> 12:12I know you're not a clinician,
12:14 --> 12:17but thinking about how different drugs
12:17 --> 12:19get metabolized in men versus women,
12:19 --> 12:22how different drugs might
12:22 --> 12:26affect the immune system in different
12:26 --> 12:29people may actually potentially have an
12:29 --> 12:32impact in terms of how they're treated.
12:32 --> 12:34Is that kind of where your
12:34 --> 12:37research is heading in terms of
12:37 --> 12:38highlighting these differences?
12:39 --> 12:40Yeah, exactly.
12:40 --> 12:43And you know, some of the research
12:43 --> 12:46that we're doing at the moment is
12:46 --> 12:49actually looking at some of the
12:49 --> 12:52in vitro data that has
12:52 --> 12:54been generated on the
12:54 --> 12:56genomes of various different colorectal
12:56 --> 12:58cancer cell lines that come from males
12:58 --> 13:01and females and looking at how the
13:01 --> 13:03drugs can actually work in these cell lines.
13:03 --> 13:06And we do see that there are sex differences
13:06 --> 13:09in how effective these drugs may be.
13:09 --> 13:12So my PHD student we have in the lab
13:12 --> 13:15is currently working on this as part
13:15 --> 13:17of her dissertation, thesis.
13:17 --> 13:19But you know,
13:19 --> 13:21what we hope to do is to then translate
13:21 --> 13:23these findings that we have in the
13:23 --> 13:25cell lines eventually into looking at,
13:25 --> 13:28you know, if we see the same effect in
13:28 --> 13:30patients by sex and gender as well.
13:31 --> 13:33Fantastic. Well, we're going to take
13:33 --> 13:35a short break for a medical minute.
13:35 --> 13:36But please stay tuned
13:36 --> 13:39to learn more about the role of forever
13:39 --> 13:40chemicals and cancer metastasis,
13:40 --> 13:43a topic we'll get more into right
13:43 --> 13:45after the break with my guest,
13:45 --> 13:46Doctor Caroline Johnson.
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14:52 --> 14:55You're listening to Connecticut Public Radio.
14:55 --> 14:56Welcome
14:56 --> 14:58back to Yale Cancer Answers.
14:58 --> 14:59This is Doctor Anees Chagpar
14:59 --> 15:01and I'm joined tonight by my guest,
15:01 --> 15:03doctor Caroline Johnson.
15:03 --> 15:07We're talking about the role of
15:07 --> 15:10forever chemicals in cancer metastases.
15:10 --> 15:12Before the break, Caroline,
15:12 --> 15:15we were talking about the work
15:15 --> 15:18that your lab is doing in terms of
15:18 --> 15:20understanding cancer metabolism,
15:20 --> 15:24how these cancers kind of use energy
15:24 --> 15:27and various metabolites to really,
15:27 --> 15:29you know, do their work as it were
15:29 --> 15:32and the differences that we see
15:32 --> 15:34in different populations based on
15:34 --> 15:36either gender or exposures, etcetera.
15:36 --> 15:39Now one of the things that your
15:39 --> 15:42lab has been looking at is this
15:42 --> 15:44concept of forever chemicals.
15:44 --> 15:46Can you define what that is and
15:46 --> 15:48talk a little bit more about
15:48 --> 15:50the work that your lab has been
15:50 --> 15:52doing looking at these?
15:53 --> 15:55Yes. So forever chemicals are
15:55 --> 15:58sort of another name for these
16:00 --> 16:03polyfluoroalcohol substances or PFAS.
16:03 --> 16:06And there's been a lot of media
16:06 --> 16:08attention about these recently because
16:08 --> 16:10they have been linked to various
16:10 --> 16:12health effects including cancer.
16:12 --> 16:14And what these are,
16:14 --> 16:17are synthetic chemicals that have very
16:18 --> 16:20strong carbon and fluorine atom bonds,
16:20 --> 16:23which means that they're very difficult
16:23 --> 16:26to break down and they stick around
16:26 --> 16:28in the environment and in our bodies
16:28 --> 16:29for a very long period of time.
16:29 --> 16:31And they have been found in,
16:31 --> 16:33you know, blood samples from
16:33 --> 16:36humans and also in tissues as well
16:36 --> 16:38such as the liver and the lung.
16:38 --> 16:39And you know,
16:39 --> 16:42they are the general sort of exposure
16:42 --> 16:45that an individual may have that would
16:45 --> 16:47come from potentially their drinking
16:47 --> 16:50water or from dietary sources as they
16:50 --> 16:52are used to make non stick surfaces.
16:52 --> 16:54So you would find them perhaps
16:54 --> 16:56on a non stick frying pan.
16:56 --> 16:58They are present on the inside
16:58 --> 17:00of microwave popcorn.
17:00 --> 17:02They're even present on waterproof cosmetics
17:02 --> 17:06and in some types of dental flosses as well.
17:06 --> 17:08And there is also greater concern for
17:08 --> 17:10those who may be occupationally exposed,
17:10 --> 17:11such as firefighters,
17:11 --> 17:14as it's present in the firefighting
17:14 --> 17:15foam as well.
17:15 --> 17:17And it really is unfortunately,
17:17 --> 17:20you know, everywhere in our supplies
17:21 --> 17:26So they are for me an area that I've
17:26 --> 17:28been wanting to look into because
17:28 --> 17:30they have had this link to cancer,
17:30 --> 17:31particularly kidney cancer,
17:31 --> 17:33but there have been some studies
17:33 --> 17:35that have shown that they are
17:35 --> 17:38also linked to certain types of
17:38 --> 17:39inflammatory bowel diseases.
17:39 --> 17:42So we were interested to look to
17:42 --> 17:44see if any of these chemicals have
17:44 --> 17:46been linked to colorectal cancer
17:46 --> 17:49etiology or in more so in prognosis
17:49 --> 17:52of the patient as we know they could
17:52 --> 17:54be linked to metabolic effects
17:54 --> 17:56and also immune system effects.
17:56 --> 17:58And in the literature we had
17:58 --> 18:00a deep dive into the literature
18:00 --> 18:02of the link between PFAS,
18:02 --> 18:04these forever chemicals, and colorectal
18:04 --> 18:06cancer as part of a project by an
18:06 --> 18:09MPH student in our lab last year.
18:09 --> 18:10And we found there was very few
18:10 --> 18:12papers that had looked at this
18:12 --> 18:14association and when they had looked
18:14 --> 18:16at the association there was very
18:16 --> 18:17contradictory findings in the literature.
18:17 --> 18:19So this is something we wanted
18:19 --> 18:20to look into within our
18:20 --> 18:22samples in vitro
18:22 --> 18:24at the moment to see if there
18:24 --> 18:25was any potential effects.
18:27 --> 18:29So, tell us more about that.
18:29 --> 18:31What did you find?
18:31 --> 18:34I mean clearly when you start
18:34 --> 18:36talking about these chemicals that
18:36 --> 18:38are very difficult to break down,
18:38 --> 18:39that hang around in the body
18:39 --> 18:41for a long period of time and
18:41 --> 18:43that are essentially everywhere.
18:43 --> 18:45I mean we just think
18:45 --> 18:47about what we've done this morning.
18:47 --> 18:50We might have used a non stick
18:50 --> 18:52frying pan to make some breakfast,
18:52 --> 18:54put some coffee in the microwave
18:54 --> 18:56and maybe last night enjoyed
18:56 --> 18:57some microwave popcorn.
18:57 --> 18:59We are ingesting these
18:59 --> 19:01chemicals all of the time.
19:01 --> 19:04So what are your data showing in
19:04 --> 19:07terms of whether these chemicals
19:07 --> 19:09actually get from these surfaces
19:09 --> 19:13into our bodies and to what
19:13 --> 19:15degree and more importantly,
19:15 --> 19:19the link or lack thereof of these
19:19 --> 19:22chemicals to the development of cancer?
19:23 --> 19:26Yes, so the first set of experiments that
19:26 --> 19:28we've done have been done in vitro.
19:28 --> 19:29So these are cell lines
19:29 --> 19:30that are grown in the lab.
19:30 --> 19:32So we'd like to preface this that
19:32 --> 19:34we haven't looked in human samples
19:34 --> 19:36or in animal models right now to
19:36 --> 19:38see if we see the same effect.
19:38 --> 19:41But what we saw in the cancer cell lines
19:41 --> 19:43was surprising and quite concerning.
19:43 --> 19:46So we used 2 two of these chemicals,
19:46 --> 19:47PFOS and PFOA,
19:47 --> 19:50And they have actually recently
19:50 --> 19:53been classified as class one and
19:53 --> 19:55Class 2B carcinogens by IARC,
19:55 --> 19:58which is an agency of the WHO.
19:58 --> 20:00And what we did was to
20:00 --> 20:02do a dose response study.
20:02 --> 20:04So we took low levels and high levels
20:04 --> 20:06of these chemicals and we applied
20:06 --> 20:08them to colorectal cancer cell
20:08 --> 20:11lines that were growing in the lab.
20:11 --> 20:13And these cell lines were derived
20:13 --> 20:16from a female patient and one of the
20:16 --> 20:18cell lines contains AK res mutation
20:18 --> 20:20that's commonly found in about
20:20 --> 20:2340% of colorectal cancer patients.
20:23 --> 20:25And so we don't see the cell
20:25 --> 20:26lines with these chemicals.
20:26 --> 20:28And the first striking observation that
20:28 --> 20:31we made was that when these cell lines
20:31 --> 20:32were given high doses of these chemicals,
20:32 --> 20:35so those seen by potentially
20:35 --> 20:36occupational exposure,
20:36 --> 20:39so from a firefighter that these cells
20:39 --> 20:41started to move away from each other.
20:41 --> 20:43So it looked like they
20:43 --> 20:44had increased motility.
20:44 --> 20:46And at first we weren't sure whether
20:46 --> 20:48this was something related to
20:48 --> 20:50potentially increased growth of the
20:50 --> 20:53cells or even death of the cells.
20:53 --> 20:54But what we found was that the
20:54 --> 20:56cell numbers were not increasing
20:56 --> 20:57and the cells weren't dying,
20:57 --> 20:58they were moving.
20:58 --> 21:01So we wanted to validate this to make
21:01 --> 21:03sure this was what we were seeing.
21:03 --> 21:06So we repeated the experiment many times,
21:06 --> 21:09but then we tried two different assays
21:09 --> 21:11which can evaluate potential metastases.
21:11 --> 21:14So one is called a wound healing assay and
21:14 --> 21:17the other one is called a transwell assay.
21:17 --> 21:19And what we found was that the cells did
21:19 --> 21:22move when we applied these higher doses
21:22 --> 21:25of PFOS and PFOA to the cell lines.
21:25 --> 21:27And then we did two follow up experiments.
21:27 --> 21:30One was at a protein level to see
21:30 --> 21:32if there were known biomarkers of
21:32 --> 21:35metastasis that were increased with
21:35 --> 21:37or were changed with application
21:37 --> 21:40of these PFOS to the cell lines.
21:41 --> 21:43And indeed we did see these change as well.
21:44 --> 21:45And then we looked at the metabolism
21:45 --> 21:48of the cell line and we saw
21:48 --> 21:50again when we applied PFOS and P4A
21:50 --> 21:52to the cell lines that the metabolism
21:52 --> 21:55changed in a way that indicated
21:55 --> 21:58migration of the cells or metastasis.
21:58 --> 22:00So all of these four things together
22:01 --> 22:04sort of led us to the hypothesis that
22:04 --> 22:06at high levels of PFOS exposure,
22:06 --> 22:10it's possible that the colorectal
22:10 --> 22:13cancer cells can migrate and metastasize.
22:15 --> 22:18So a couple of questions there.
22:18 --> 22:21So the first question is,
22:21 --> 22:23it sounds like you were using
22:23 --> 22:24cell lines that already had,
22:24 --> 22:27for example, a KRas mutation,
22:27 --> 22:30and that you were looking at cancer
22:30 --> 22:32cells themselves and found that
22:32 --> 22:35they were more likely to move when
22:35 --> 22:38exposed to these chemicals in
22:38 --> 22:41cell lines or in people who don't
22:41 --> 22:44necessarily have a cancer already.
22:44 --> 22:46Do these chemicals cause that
22:46 --> 22:50kind of a cancer or is this really
22:50 --> 22:53more so a risk of metastasis
22:53 --> 22:56in people who already have cancer?
22:57 --> 23:00So based on the findings in our research,
23:00 --> 23:03the sort of only hypothesis I can make
23:03 --> 23:06at the moment is that this would be an
23:06 --> 23:09issue for those that already have cancer.
23:09 --> 23:12I haven't seen,
23:12 --> 23:15as I said initially, that
23:15 --> 23:17the literature right right now surrounding
23:17 --> 23:20the effects of these chemicals in
23:20 --> 23:22colorectal cancer is really inconsistent.
23:22 --> 23:25So at the moment we are concerned about
23:25 --> 23:27how these chemicals could actually be
23:27 --> 23:30causing the cell lines to metastasize
23:30 --> 23:33because as you know at the
23:33 --> 23:36latest stage that the cancer is at,
23:36 --> 23:38the harder it is to treat.
23:38 --> 23:40So we don't want to be having you
23:40 --> 23:42know the tumors to get to the
23:42 --> 23:45metastatic stage.
23:45 --> 23:47And what we've seen as well through our
23:47 --> 23:49results is that this could be
23:49 --> 23:51potentially due to a number of things,
23:51 --> 23:53it could be altering these
23:53 --> 23:57proteins that could be initiating metastasis.
23:57 --> 24:00We also see from some predictive models
24:00 --> 24:03that it could be linked to inflammation
24:03 --> 24:06and immune modulation as well.
24:06 --> 24:09So there is definitely a lot for
24:09 --> 24:10us to investigate.
24:10 --> 24:12This has just been
24:12 --> 24:14one set of cell lines and
24:14 --> 24:16grown in the lab.
24:16 --> 24:18So that's something that we are looking
24:18 --> 24:21to investigate in the next year.
24:22 --> 24:24The second question
24:24 --> 24:27is with regards to the dose.
24:27 --> 24:29So you had mentioned people or
24:29 --> 24:32cell lines that were exposed to high
24:32 --> 24:35doses of these chemicals had this effect.
24:35 --> 24:37And so the question is,
24:37 --> 24:40as you mentioned something that
24:40 --> 24:43you would see more in people who were
24:43 --> 24:45occupationally exposed like firefighters
24:45 --> 24:48or is this something that
24:48 --> 24:50we would see even in people who were
24:50 --> 24:52exposed with all of the other ways that
24:52 --> 24:55we are exposed to these chemicals.
24:55 --> 24:57So for example,
24:57 --> 24:59would you advise cancer
24:59 --> 25:01patients who potentially have nonstick
25:01 --> 25:04frying pans to get rid of their
25:04 --> 25:06nonstick frying pans or not use the
25:06 --> 25:09microwave or not have microwave popcorn.
25:09 --> 25:13I mean what is the exposure related
25:13 --> 25:16to those everyday exposures versus
25:16 --> 25:18the occupational exposure?
25:19 --> 25:20Yes, so as I mentioned,
25:20 --> 25:23we looked at those lower doses as well.
25:23 --> 25:25So those that are more environmentally
25:25 --> 25:28relevant that an individual would be
25:28 --> 25:30exposed to through drinking water and we
25:30 --> 25:33didn't see that the cells were spreading,
25:33 --> 25:35but some follow up experiments in
25:35 --> 25:38our laboratory where we've looked
25:38 --> 25:40at very low levels of now about
25:40 --> 25:438 different types of PFAS
25:43 --> 25:46what we've seen is that the cell
25:46 --> 25:48lines are actually starting to grow.
25:48 --> 25:51So they're starting to increase in number
25:51 --> 25:55at these lower levels of exposure.
25:55 --> 25:56But when we get to the higher
25:56 --> 25:58levels of exposure,
25:58 --> 25:59we don't see this cell growth,
25:59 --> 26:01we see the cell motility.
26:01 --> 26:04So what's kind of really fascinating
26:04 --> 26:06about these chemicals and their effects
26:06 --> 26:09in cancer is that they can actually to
26:09 --> 26:11us in the lab appear to have different
26:11 --> 26:14effects at low versus high levels.
26:14 --> 26:16And I think this is something
26:18 --> 26:20really important to investigate further.
26:24 --> 26:26In terms of reducing exposure in general,
26:26 --> 26:28I think as you mentioned about
26:28 --> 26:31the non stick frying pans,
26:31 --> 26:34these do tend to be coated in some
26:34 --> 26:37of these PFAS chemicals and some of the older
26:38 --> 26:40legacy PFAS have been
26:40 --> 26:41removed but they've been replaced
26:41 --> 26:43by other types of PFAS.
26:44 --> 26:46My advice there would be to go back
26:46 --> 26:48to using a a good old
26:48 --> 26:52iron skillet and a seasoned skillet.
26:52 --> 26:54That's what I use in my household now.
26:54 --> 26:57It makes a really good fried egg,
26:57 --> 26:59to try and reduce NOTE Confidence: 0.686547544
26:59 --> 27:01exposure that way.
27:01 --> 27:02But yeah,
27:02 --> 27:04I think more knowledge in this area is
27:05 --> 27:06really vital for cancer patients
27:06 --> 27:08and I think it has been lacking.
27:11 --> 27:14The other question is,
27:14 --> 27:16if we step back and we look
27:16 --> 27:19from an epidemiologic standpoint,
27:19 --> 27:22have we seen the similar kind of effects?
27:22 --> 27:25So are firefighters with
27:25 --> 27:27colorectal cancer, for example,
27:27 --> 27:30more likely to have distant metastatic
27:30 --> 27:32spread than non firefighters?
27:32 --> 27:35Do we have that kind of epidemiologic data?
27:36 --> 27:39That isn't data that I'm aware of right now,
27:39 --> 27:42but I think that's a really
27:42 --> 27:44important thing to look into.
27:44 --> 27:48There was a study out recently that I
27:48 --> 27:51found was quite interesting and they saw
27:51 --> 27:53that individuals that had been
27:53 --> 27:56diagnosed with cancer such as uterine,
27:56 --> 27:57ovarian, and melanomas,
27:57 --> 27:59they did have high levels
27:59 --> 28:01of PFAS in their blood,
28:01 --> 28:03but it didn't specify in that study
28:03 --> 28:05what their occupation was.
28:05 --> 28:07But I think looking
28:07 --> 28:08at firefighters it is
28:11 --> 28:13really important to try and
28:13 --> 28:15mitigate their potential
28:15 --> 28:17exposure to these chemicals.
28:18 --> 28:20Doctor Caroline Johnson is an
28:20 --> 28:22associate professor of epidemiology
28:22 --> 28:24and environmental Health Sciences at
28:24 --> 28:26the Yale School of Public Health.
28:26 --> 28:28If you have questions,
28:28 --> 28:30the address is canceranswers@yale.edu.
28:30 --> 28:33And past editions of the program
28:33 --> 28:35are available in audio and written
28:35 --> 28:36form at yalecancercenter.org.
28:36 --> 28:39We hope you'll join us next week to
28:39 --> 28:41learn more about the fight against
28:41 --> 28:42cancer here on Connecticut Public Radio.
28:42 --> 28:45Funding for Yale Cancer Answers is
28:45 --> 28:47provided by Smilow Cancer Hospital.

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The Role of ‘Forever Chemicals’ in Cancer Metastasis with guest Dr. Caroline Johnson February 4, 2024