December 1, 2014

Metabolic Theory of Cancer: Cells Behaving Badly




If you’re just tuning in, you have landed on a series in which we are exploring the metabolic origins theory of cancer. To find out what this means, take a minute to visit the introductory post. (You can also just read this book review on Amazon for a quick version of what this is all about.)

In this first installment of getting into all this, I think it’s a good idea for us to take a look at some of the ways in which cancer cells distinguish themselves from healthy cells.

  • Generally speaking, they don’t die. Healthy cells undergo a kind of programmed suicide when their parts & pieces are damaged or worn out. They’re not supposed to live forever. When they outlive their usefulness, they make a graceful exit. This programmed cell death is called apoptosis, and it is largely absent in cancer cells. Think of it as the reverse Darwin Awards: instead of taking themselves out of the gene pool by doing something really stupid, cancer cells are absolute geniuses at keeping themselves in itforever. (Until, that is, they grow and spread enough of themselves that they kill their “host,” which, when you think about it, actually does get them a Darwin Award.) Seriously, though, instead of dying as programmed, like good little cells, cancer cells just multiply, and multiply, and multiply, and grow and grow, and spread and spread. 




  • They don’t exhibit contact inhibition. When healthy cells come into contact with other cells—think of it like a person bumping up against someone else in a crowded elevator—those cells stop getting larger. Their growth is inhibited by contact with surrounding cells on all sides. Cancer cells exhibit no such inhibition. They grow and grow and multiply and multiply, ignoring all signals to stop growing and multiplying. It’s like a crowded bus at rush hour, but instead of closing the doors and driving away, the driver just keeps letting people pile on and pile on. There’s no end to how many people are going to stuff themselves onto that bus, and there’s no end to how cancer cells will keep growing and dividing. This is how tumors become tumors—they’re just gigantic masses of cells that keep getting more gigantic.

  • They have all kinds of weird mutations in their DNA. And the thing is, not all cancer cells exhibit the same kinds of mutations. There are both INTERtumoral and INTRAtumoral heterogeneity. That is big-word-speak for saying that the genetic mutations seen in cancer differ both from one kind of tumor to another, as well as within the same tumor, within the same person. Meaning: the mutations seen in breast cancer differ from those seen in lung cancer, which differ from those seen in prostate cancer, or skin cancer, or any other kind of cancer. Also meaning: in a cancerous tumor in one individual, the mutations in some cells are different from the mutations in other cells. In a single tumor, from a single individual, the mutations to the nuclear DNA differ from cell to cell. As Travis Christofferson summed it up in his book, “Most solid tumors display a hurricane of genetic chaos.” (p.184) This is just one reason, among many, why treatments aimed at these genetic mutations have failed for the most part. You would have to invent a separate drug/therapy targeting each individual mutation. We will revisit this a few posts down the line.

  • Tumors stimulate the creation of their own blood supply. Like any other living thing trying to survive in the world—particularly something that does everything it can to evade death—cancer cells need to eat. They need a fuel supply, and in order to ensure they get it, tumors whip out this neat party trick called angiogenesis—science-speak for what I just said: creating their own, new blood vessels, meant to specifically supply them with nutrients. Damn, cancer cells are wily little S.O.B.s, no?

Migration: Fine when birds do it;
terrible when cancer cells do it.
  • They spread from their site of origin to other places in the body. This is metastasis. Healthy cells generally stay where they’re supposed to: hepatocytes stay in the liver; enterocytes stay in the small intestine; pancreatic cells stay in the pancreas. Cancer cells, on the other hand, have wanderlust. They’re not content to stay put. Like randy teenagers, they can sneak out of their tissue of origin, hitch a ride (via the bloodstream or lymphatic system), and end up at the unsupervised party three organs away, where they bring the booze and wreak havoc will take root and establish yet more cancer. This is why someone with cancer can have multiple tissues and organ systems affected, even though the cancer always starts somewhere. It’s also part of the reason treating cancer is a bit like playing that old arcade game, Whack-a-Mole. As soon as you target the cancer in one spot and maybe even get rid of it, it pops up somewhere else. Remember this whack-a-mole analogy; we will use it often. (You can already see how it applies to treating cancer via targeting the aforementioned genetic mutations. Develop a drug that corrects one mutation, and there are still potentially thousands of others to go after.)

  • They show different levels of differentiation. Within a cancerous mass, some cells will resemble mature cells of the tissue type they came from (for example, a prostate cell, or an ovarian cell), while others will be undifferentiated or “poorly differentiated” – they will lack some of the physical structures and biochemical features of the cells where they originated. Malignant tumors “have abnormal-looking cells and may lack normal tissue structures.” And the less differentiation there is (the more abnormal cells), the faster the cancer tends to grow and spread

The best way I can explain differentiation is to say that poorly differentiated/undifferentiated cells resemble embryonic cells more than mature cells with a specific purpose. When we are still tiny sacks of cells in our mother’s womb, our cells are mostly undifferentiated. Eventually, they will receive programmed signals to migrate and change and differentiate into liver cells, retinal cells, cardiac muscle cells, etc. But before that happens, they are more like primordial “things” just kinda hanging out until someone tells them what they’re supposed to be. And as we all know, when you’ve got a group of people (cells) just sitting around without a sense of purpose, they are likely to get into trouble. Think of that old saying: idle hands are the devils workshop.

So a cancer cell that originates in, say, the breast tissue, doesn’t always look or act like a breast tissue cell. It might even start to look or act like some other type of cell, which is why there are reports of teeth, hair, bone, and other body structures being found inside tumors in organs and tissues completely unrelated to teeth, hair, and bones. This is called teratoma, and it shows even more just how wacky and truly weird cancer is. (I am absolutely not making this up.) Note: teratomas are not unique to cancer. Sometimes, wacky things happen in our bodies, regardless of anything else. (Such as this benign ovarian tumor that sprouted hair and teeth!)


There are three other main hallmarks of cancer cells, but because they are BIGGIES—so big, in fact, that they will be the focus of pretty much the rest of this entire series—I will save them for their own posts. But in order to understand why they are such biggies, we need to lay some groundwork first, by taking detours through how cells metabolize fuels to generate energy, and also visit the structure and function of mitochondria, our cells’ main power plants. After all, if we are looking at cancer as a metabolic disease, then weve got to familiarize ourselves with cellular metabolism.




P.S. If this is seeming a little dry, please, please stay with me. I promise you, things are going to get fascinating. But we really do need to do a little wading through the biochemical weeds first.


Continue to the next post: Cellular Energy Generation 1 - Glycolysis





Remember: Amy Berger, M.S., NTP, is not a physician and Tuit Nutrition, LLC, is not a medical practice. The information contained on this site is not intended to diagnose, treat, cure, or prevent any medical condition.

3 comments:

  1. Not at all dry. You have created an excellent picture of a normal, healthy cell who forgets how to behave itself and as a result looses its way. All it knows is a drive to survive at any cost.

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  2. Interesting. Keep it coming.

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  3. Good. You have a nice writing style, clear and to the point, not without humour.

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