I Had Cancer And Wonder If Stem Cells Were To Blame

Paul Knoepfler

I confess.

I had cancer.

And stem cells might be to blame!

At the relatively young age of 42, I was diagnosed with what is supposed to be an older man’s disease: prostate cancer.

How could this happen to me? It could be the fault of stem cells.

No, I don’t mean some rogue stem cells created in my own lab that attacked me, but rather I’m talking about a few of my own perhaps imperfect stem cells that might have gone rogue.

You see scientists are realizing that for many, but not all cancers, a unique type of stem cell called a “cancer stem cell” might be to blame.

As we live, our cells are not simply sitting there, even if we are. They are doing stuff like making our hearts beat, our minds think (at least some of us), and so on. For some if not almost all tissues of our bodies, cells have to be replaced and stem cells make this happen.

Think of subs in a football game.

In fact some of our cells get pretty beaten up or even killed doing their jobs. Imagine a quarterback who has just been steamrolled by a 350 lb. linebacker. That happens to some of our cells too, except instead of a linebacker it might be radiation from the world we live in, or a free radical molecule generated in our bodies, or some other cellular linebacker.

And stem cells are like the quarterbacks of our bodies. They direct much of what goes on. If they get hurt, we could be in big trouble. A lot of quarterbacks get concussions, a condition that these days we are realizing can have serious long-term health consequences including brain damage. For a cell, its brain is its nucleus, where its precious DNA is tucked away. Most often when stem cells get injured, they suffer damage to their brain, to their nucleus in the form of mutations.

The problem with damaged stem cells is more complicated, interesting, and dangerous than you might think first hand. Because you see, when a stem cell suffers brain damage in the form of a mutation, sometimes it is not just out of commission (i.e. dead). You do not always simply lose this valuable cell. Sometimes, there are worse consequences.

Imagine in a football game if your star quarterback gets hammered and has to leave the championship game. That’s horrible, right?

‘What could be worse?’, you think. I’ll tell you.

Imagine your quarterback gets his clock cleaned, but instead of leaving the game he secretly starts helping the other team. Throwing interceptions, fumbling, tripping his own players….that is far worse than him leaving the game.

The same kind of thing can happen inside of us with our stem cells. When damaged, sometimes they do not leave the game (undergo apoptosis), but go on to play against us as cancer stem cells. It is the ultimate betrayal because the new goal for them is nothing short of killing us.

These extreme Benedict Arnolds, cancer stem cells, play a role in many cases of prostate cancer so I wonder -- might they be to blame for my cancer? Wouldn’t that be ironic if I, as a cancer and stem cell biologist, got cancer because my stem cells turned against me?

Think Anakin Skywalker turning into Darth Vader.

That’s one of the problems with stem cells. They are so powerful that if they do turn to the dark side, we are in trouble.

Admitting publicly that I have cancer is a risk for me. People do view you differently when you have had a major illness such as cancer, but for the most part, I’ve gotten very positive support from both the scientific and non-scientific communities that I am part of these days. I think part of the reason is that cancer touches everyone in one way or another. If you want to read more about my experiences as a cancer scientist turned cancer patient and cancer survivor, you can read some of blog entries here and here.

I am 20 months out from surgery (knock on wood) and in full remission...therefore so far I am doing well. I know the cancer could come back, but that's just life. Anyone can get diagnosed with cancer any day as well. You have to live your life anyway.

Of course I don’t know that stem cells had anything to do with me getting cancer. In fact I hope they didn’t.

But I’ll never know for sure of course and sometimes I wonder...

Comments

Castration-resistant Nkx3.1-expressing cells were implicated in a study in 2009 (mice, anyway) - the CARNs led to prostate cancer if certain tumor suppressor genes in the cells were inactivated. A few months back in Cell Stem Cell similar studies found the same in breast cancer.

What different reaction do you get regarding the cancer thing? The Big C used to seem like a death sentence but now it is a different animal...or do people still think all cancer is terminal? The great promise of hESC might be making it a lot more manageable, like diabetes.

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Hank Campbell | 07/25/11 | 00:32 AM

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From what I understand there are likely cancer stem cell-like cells in prostate cancer in people, but I'm curious to see how the field develops and if that has any meaning for treatment or prevention.
People generally have reacted supportively to the Big C.

A lot of people did not know what to say at the beginning of my experience, which is fine. I was not judging them. It is awkward.

A few were idiots, but they were rare. Career-wise, I don't know long term what the impact might be, but so far in the nearly 2 years since my surgery, I have not seen any issues.

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Paul S. Knoepfler, Ph.D. Associate Professor UC Davis School of Medicine http://www.ipscell.com

Paul Knoepfler | 07/25/11 | 10:55 AM

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I would be as baffled as anyone on a committee worrying about cancer in remission as I would blogging. In the time you have been reading blogs, things changed a lot. In 2006, there was one blogging site and it was all crazy people in science ranting about politics and religion but after we came along and people saw it could instead be legitimate outreach with no editors dumbing it down or telling people what to write about, it is quite mainstream, with Forbes, Discover, Scientific American and even National Geographic all hosting science blogging divisions. We're just the only independent one, not owned by a magazine or with any taxpayer funding, so that makes us more awesome. But it can't be a career knock to have a popular blog here. Carl Wieman has articles here, and it isn't like they took away his Nobel prize or he didn't get a job in the Obama administration because of it.

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Hank Campbell | 07/25/11 | 11:08 AM

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Paul, I read your link to your other blog in which you said :-

Some of my colleagues do not approve of my blogging and they have bluntly told me their opinion in that regard. They honor the invisible wall between scientists and patients. They take the somewhat old-fashioned perspective that scientists outside the confines of the lab or scientific conferences, should basically keep their mouths shut.

Others tell me frankly that even though they can see the positive in academic scientists blogging, they think I am taking a risk career-wise. They worry that I might accidentally say something politically incorrect. They tell me that perhaps I might make other scientists or funding agencies mad by what I say.

Don’t I worry about that? Yes, I do. These risks are very real and I’ve already taken some heat. I’m sure there is also risk in my telling my story today in this blog post that I have had cancer as there can be discrimination against cancer survivors.

I take these risks with open eyes because I feel strongly that biomedical scientists such as myself need to communicate to a broad audience as patient advocates. And as a cancer survivor I have even more responsibility in that regard.

I would like to commend you for taking these brave risks and responsibilities seriously and for sharing this information with the public in your blogs. I think that I now maybe understand why you keep saying that you are confessing, because confession usually revolves around a need to escape from and/or be absolved from feelings of guilt, caused maybe by these elitist behaviours and practices that often result from professional embedment, culture and fear.

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Helen Barratt | 07/25/11 | 04:51 AM

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Thanks, Helen. I appreciate your supportive and insightful words. I think so much of science is about communication, but in many ways scientists as a group are not great communicators when it comes to the big picture. Most scientists are great at "public speaking" meaning giving seminars or talking in front of an audience of hundreds, but on the other hand most are not good at actually saying what they believe in public or advocating for a position.

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Paul S. Knoepfler, Ph.D. Associate Professor UC Davis School of Medicine http://www.ipscell.com

Paul Knoepfler | 07/25/11 | 10:58 AM

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Paul, as I mentioned on my rather massive, probably pseudoscience, Frankenstein blog about the Earth's weakening geomagnetic force and possible polar reversal, many scientists are simply not allowed to make these comments publicly because they have signed confidentiality agreements within the large organisations they work.

Most large organisations like CERN for example employ PR companies and staff who carefully manage the release of data and information to the public. Psychology and journalism are both producing large numbers of public relations staff who handle these correspondences with the public and often even prevent the employees from publicly commenting without fear of retribution.

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Helen Barratt | 07/25/11 | 17:16 PM

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One thing that I am confused about is how some cancers seem to have a viral or contagious component. For example if I understand it correctly nuns rarely get cervical cancer as this is transmitted sexually by men who have genital warts and presumably nuns rarely if ever have sex.

Likewise the tasmanian devil is being driven to extinction by a deadly facial cancer that is transmitted by a bite from another tasmanian devil who is already infected. Is it possible that by working and studying these stem and cancer cells for many years you were somehow accidentally infected with prostate cancer?

Finally I have read somewhere that there are often clusters of women with breast cancers and that some scientists were researching the possibility that these clusters of women were somehow passing breast cancer to eachother, is that at all possible do you think?

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Helen Barratt | 07/25/11 | 10:21 AM

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The cancer you mention in tasmanian devils, which also can attack dogs, is very unusual. It is actually contagious at the cellular level and is thought to be an immortal, independent biological entity. Very creepy. I blogged about it here. It is called CTVT.

Certainly HPV causes cervical cancer. More generally, viruses are can cause cancer in people for sure, but it is a relatively rare phenomenon...at least scientists think it is at this point. Perhaps it is more common than we realize. I know there was some story about prostate cancers often containing some obscure virus, but I am not sure that was reproducible.

I doubt that I got infected with a virus or cancer during my research career, although I suppose it is formally possible. There are a number of hazards that many of us scientists are exposed to including radioisotopes, chemicals, synthetic viruses, but I think it takes a bunch of stuff going wrong to cause a cancer in most cases. Some of it is just plain bad luck.

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Paul S. Knoepfler, Ph.D. Associate Professor UC Davis School of Medicine http://www.ipscell.com

Paul Knoepfler | 07/25/11 | 18:00 PM

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but I think it takes a bunch of stuff going wrong to cause a cancer in most cases

I'm interested in why you say this? Isn't it possible for just one thing to go wrong to make one cell mutate it into an immortal cancer cell during its cell division? That one thing being maybe either an adverse chemical, radioactive, viral or genetic factor?

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Helen Barratt | 07/25/11 | 17:23 PM

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This is a great question and one I have been pondering for a long time.
The answer for human cancer is generally "no", one mutation is not enough. You need multiple "hits" as we call them to lead to cancer development.

In the lab, human cells are notoriously difficult to "transform" into cancer cells. We seem to have better protection against cancer than some other species such as rodents. You might ask "well, humans sure seem to get more than their share of cancer". That might be true, but the overwhelming majority of human cancer occurs after age 30, an age after which we weren't really supposed to be surviving from a broad, evolutionary perspective.

Getting back to the idea of one mutation leading to cancer, that "no" is a bit qualified from a practical real world kind of setting because you see none of us are what we'd call "wild type". We are born with mutations inherited from our parents and also with cancer predisposition genomic states. Then even before we are born we start the continual addition of more mutations just from being exposed to a variety of mutagens.

Another point is that we do not really know in the real world outside the lab how cancers begin and evolve. By the time we all analyze them, they are full of mutations, but maybe there are some very powerful single mutations that ultimately start the ball rolling.

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Paul S. Knoepfler, Ph.D. Associate Professor UC Davis School of Medicine http://www.ipscell.com

Paul Knoepfler | 07/25/11 | 18:07 PM

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Just as a completely speculative question out of left field. Have we ever seen cellular behavior similar to cancers occur in single-celled organisms (i.e. colonies)? In other words, is there anything to indicate that a colony of single-celled organisms can be disrupted by cells of the same species suddenly becoming disruptive to that colony?

I realize that's probably a bit vague, but I'm envisioning the regulatory mechanisms that are necessary in order to maintain cooperation within a multi-celled organism, and so I'm speculating about any mechanism that might disrupt that process and allow cells to "go rogue".

Gerhard Adam | 07/25/11 | 19:09 PM

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Gerhard-fantastic question!To my knowledge, the answer is "no". Single celled organisms have not been observed to exhibit dramatically unregulated growth of the kind seen in cancer in "higher' organisms.

Why?

It's very unclear. One notion is that the evolutionary advance to multi-cellular-ism opened the door to cancer. It was a trade off. However, it is possible that all single-celled organisms already intrinsically behave like cancer cells because they grow rapidly and at the expense of any other living things around them. I think this is an interesting idea.

Single celled organisms such as yeast have much of the same molecular machinery as us. Even fruit flies are thought to not get cancer, although there is some debate about that.

I am not sure if people have tried to force yeast to behave more like cancer--I'll have to do some research on that.

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Paul S. Knoepfler, Ph.D. Associate Professor UC Davis School of Medicine http://www.ipscell.com

Paul Knoepfler | 07/25/11 | 19:27 PM

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I blogged about it here. It is called CTVT.

BTW Paul, your link to the tasmanian devil CTVT blog doesn't seem to be working.

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Helen Barratt | 07/25/11 | 17:31 PM

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I think the link is fixed. The full link, FYI, is:http://www.ipscell.com/2011/01/contagious-cancer-the-allograft-your-dog-doesnt-want/

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Paul S. Knoepfler, Ph.D. Associate Professor UC Davis School of Medicine http://www.ipscell.com

Paul Knoepfler | 07/25/11 | 18:01 PM

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Thanks for fixing the link in which it says :-

Fortunately, as far as scientists know, contagious cancer does not exist in humans. Thank goodness. A fascinating question is why?

Sorry, but I don't understand this? We've just agreed that men with genital warts give women a deadly cervical cancer from unprotected vaginal sex and I believe that lately this has been widened to possibly include throat cancers in both sexes caused by oral sex with people who are infected with the virus, surely that is contagious human cancer?

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Helen Barratt | 07/25/11 | 19:09 PM

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Sorry I was not clearer. It is a confusing issue.
In humans, viruses are clearly contagious. They can be spread from one person to many others. Some viruses, such as HPV16 can cause cervical and other cancers. Thus, if a person infects another person with HPV16, in theory they are in a way indirectly giving that person a highly increased risk of cancer. But not everyone infected with HPV16 will get cancer. So that's viruses that can be oncogenic being transmitted from person to person.

In the dogs and Tasmanian Devils, it is a very different situation. They can literally and directly pass on cancer to each other. Not a virus, but actual cells, cancer cells. It is the cancer itself that can be directly passed on from animal to animal.

Amazingly and frighteningly, these cancer cells seem to be able to grow in another host and are not derived from the dog that gets the cancer. They are in essence an independent organism, a horrible one that is immortal.

To my knowledge, in humans there is no evidence of cancer itself (meaning the actual cells) being transmitted from one person to another, except in the case of organ transplantation when it has definitely occurred. However, it is formally possible that it happens in immunocompromised people outside the context of organ transplantation too during sex or if someone bites someone or gets exposed to blood.

I hope this makes sense.

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Paul S. Knoepfler, Ph.D. Associate Professor UC Davis School of Medicine http://www.ipscell.com

Paul Knoepfler | 07/25/11 | 19:33 PM

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Yes this makes sense. Is it therefore also possible that an infected Tasmanian Devil or dog could bite a human or transmit the cancer in some other way to humans or are these cancers still species specific? I would have thought this was likely if the cancer cells are not in any way derived from the cells of the host animal?

Also, I read that sharks rarely get cancer because sharks and their cartilage contain an 'angiogenin inhibitor' which prevents the formation of the new blood vessels required to feed a new tumour, is that something you have tested at all and do you take shark cartilage supplements? Sorry about all these questions but its an interesting subject. I also had a potentially fatal small micronodular BCC removed from my eye socket last year and I am now hopefully in remission. It looks as though mine was caused by a black eye many years ago from an ex-boyfriend, as it appeared shortly afterwards and they can apparently be trauma induced.

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Make love not war

Helen Barratt | 07/25/11 | 23:59 PM

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Helen, best wishes to you that the BCC is a thing of the past!

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Paul S. Knoepfler, Ph.D. Associate Professor UC Davis School of Medicine http://www.ipscell.com

Paul Knoepfler | 07/26/11 | 15:32 PM

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Thanks Paul and best wishes to you that you also stay in full remission. You said in your article :-

Admitting publicly that I have cancer is a risk for me. People do view you differently when you have had a major illness such as cancer, but for the most part, I’ve gotten very positive support from both the scientific and non-scientific communities that I am part of these days. I think part of the reason is that cancer touches everyone in one way or another.

I wondered what you perceive the risk is that people incur by publicly admitting having had cancer in the past? Health insurance risk, job prospect risk or social and/or professional stigma?

In Australia skin cancers are highly prevalent and most middle-aged white people that you meet will have had some sort of skin cancer identified and/or removed; so maybe I am not perceiving the risks involved in admitting having had this potentially fatal, flesh eating skin cancer which maybe would be a risk for me to admit in America or Europe?

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Make love not war

Helen Barratt | 08/26/11 | 18:37 PM

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They are in essence an independent organism, a horrible one that is immortal.

In a sense, this seems plausible, if we take a few liberties in interpretation. If we consider that virus' are essentially capable of infecting an organism by hijacking a cell's reproductive machinery to its own ends, then it's not that far of a stretch to imagine a type of virus that actually retains the hijacked cell to continue it's growth. Being independent is exactly the type of characteristic one would expect in this kind of infection.

This is one of the things I find particularly interesting at this level, is that regardless of the complexity of the biological operations at the cellular level, it is obvious that these cells "know" what they are doing to maximize their ability to regulate and/or exploit cellular operations in large groups.

You had mentioned that single-celled organisms may already behave somewhat like cancer cells and consequently no anomalous behaviors occurred, but it seems that most bacterial colonies don't compete to the detriment of the colony unless they are severely stressed. In those cases, they resort to cannibalism rather than destroy the colony which still seems like remarkably directed behavior to self-preservation even though they are single-celled. I also have to believe that with quorum sensing we have a trait that clearly suggests that bacteria are quite capable of ensuring that they don't directly compete without regard for other members of their species and some degree of "cooperation" must exist.

Once again ... pure speculation ... it's almost as if cancer cells have lost the ability to communicate with the group and consequently they simply behave without recognizing the normal feedback they would get in such a communal group. I know I mentioned a type of "insurrection-like" behavior, but that doesn't really make any sense because the somatic evolution that drives them, doesn't ever convey any advantage, so it can't be subject to selection pressures. They will die just as readily as the host they inhabit. Therefore cancer cells can't be anything internally established by evolution ... it must either represent a breakdown in normal behavior, or it must be driven by an external agent that is capable of deriving benefit (and being selected for).

Anyway ... just speculating :)

Gerhard Adam | 07/25/11 | 20:52 PM

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