Extracellular Matrix Regulates Gene Expression & Cancer
Gene mutations are part of the process of cancer, but mutations alone are not enough to cause cancer to take hold and spread, thus threatening people’s lives through domination of precious life resources (nutrition) as well as precious real estate where other healthy cells live. Genes do become damaged and sustain mutations in some cells and not others during people’s lifetimes. An oncogene—a gene that causes tumors in animals and uncontrolled growth in cells in culture—cannot in and of itself change cells from normal to cancerous. It is the cells’ surroundings, known as its microenvironment, that contribute in some way to how cancer has occurred.
Cancer involves an interaction between rogue cells and surrounding tissue. This is the clear message that Dr. Mina Bissell, who is the director of life sciences at the Lawrence Berkeley National Lab in California (LBNL), and she is now sharing this with the world. The interactions between cancer cells and their micro and macroenvironments create a context that promotes tumor growth and protects them from immune attack or, on the other hand, prevent tumors from making any kind of beachhead so they cannot take hold or spread themselves around. Cancer cells routinely form in most people’s bodies but that does not mean they are going to succeed in capturing their host’s valuable resources so they can invade (inland so to speak) as they win their war and take our life.
What this means is that the surrounding cells and the surrounding extracellular matrix interact to shape cancer cell behaviors such as polarity, migration and proliferation. The microenvironment includes a complex scaffolding on which cells grow and develop, called the extracellular matrix. The microenvironment is what actually surrounds a cell. The extracellular matrix (microenvironment) has been shown to regulate gene expression so it has more to do with the state of cancer than the cancer cells themselves.
“If tissue architecture and context are part of the message, then tumor cells with abnormal genomes should be capable of becoming ‘normal’” if grown in a healthy microenvironment. Dr. Bissell and her students tested that hypothesis with some malignant cells, growing them on a healthy scaffolding. And yes, they were able to revert the malignant phenotype to a normal one. They could even inject the cells into mice where they didn’t cause tumors, unlike malignant cells, which would cause cancer. This, says Bissell, indicates that there is another way to look at cancer—that cancer genes are regulated by the environment around them.
Dr. Bissell’s basic idea is that cancer cells cannot turn into a lethal tumor without the cooperation of other cells nearby. It is not just the other surrounding cells but also the interstitial environment, which of course would include pH and nutrient levels being supplied by the blood. That may be why autopsies repeatedly find that most people who die of causes other than cancer have at least some tiny tumors in their bodies that had gone unnoticed. According to current thinking, the tumors were kept in check, causing no harm.
“Think of it as this kid in a bad neighborhood,” said Dr. Susan Love, a breast cancer surgeon and president of the Dr. Susan Love Research Foundation. “You can take the kid out of the neighborhood and put him in a different environment and he will behave totally differently.” She added, “It’s exciting. What it means, if all this environmental stuff is right, is that we should be able to reverse cancer without having to kill cells. This could open up a whole new way of thinking about cancer that would be much less assaultive.”
Dr. Bissell is now hailed as a hero, with an award named after her. “You have created a paradigm shift,” the Federation of American Societies for Experimental Biology wrote in a letter announcing that she had won its 2008 Excellence in Science award.
Dr. D. W. Smithers, then at Royal Marsden Hospital in London, argued that cancer was not a disease caused by a rogue cell that divides and multiplies until it destroys its host. “Cancer is no more a disease of cells than a traffic jam is a disease of cars,” Dr. Smithers wrote. “A lifetime of study of the internal-combustion engine would not help anyone understand our traffic problems.”
The death rate has barely budged for most cancers, and the gene mutation strategy so far has been a failure—a senseless one that has been used to reinforce the insane and very deadly form of medicine contemporary oncologists practice. Dr. David Agus, a conventional oncologist, agrees that cancer treatments have a shortsighted focus on individual cells.
In a yet to be published essay titled, “Catching Cancer Cells in a Deadly Crossfire,” I talk about supercharging the micro and macroenvironments with life force making it more impossible for the cancer cells to survive. In that chapter I use military terminology and imagery and we know what happens when we reinforce the troops that surround an enemy.
Cells that are in harmony move and work together to create and work toward the conditions necessary for overall health. We can turn to physics and remember what happens to a bunch of grandfather clocks on the wall. They can all be swinging in wide opposition to each other but come back a while later and they will all be swinging together. Our cells are like that, all the many trillions of them. There is coherence to the entire colony of cells until what we call cancer occurs and then that coherence begins to break down.
Chemotherapy Provokes More Not Less Cancer
Chemotherapy can cause damage to healthy cells, which triggers them to secrete a protein that sustains tumor growth and makes cancer more resistance to any further treatment. We are beginning to see clinical evidence across the board show that what happens to healthy cells during cancer treatment determines much if not the entire outcome of treatment.
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“Cancer cells inside the body live in a very complex environment or neighborhood. Where the tumor cell resides and who its neighbors are influence its response and resistance to therapy,” said senior author Dr. Peter S. Nelson, a member of the Hutchinson Cancer Center’s Human Biology Division. “Our findings indicate that the tumor microenvironment also can influence the success or failure of these more precise therapies.” In other words, the same cancer cell, when exposed to different “neighborhoods,” may have very different responses to treatment.
Researchers at the center tested the effects of a type of chemotherapy on tissue collected from men with prostate cancer, and found “evidence of DNA damage” in healthy cells after treatment, the scientists wrote in Nature Medicine in August of 2012.
The scientists found that healthy cells damaged by chemotherapy secreted more of a protein called WNT16B, which boosts cancer cell survival. The researchers observed up to 30-fold increases in WNT production! “The increase in WNT16B was completely unexpected,” said Dr. Nelson. The protein was taken up by tumour cells neighboring the damaged cells. “WNT16B, when secreted, would interact with nearby tumor cells and cause them to grow, invade, and importantly, resist subsequent therapy,” said Nelson.
Rates of tumor cell reproduction have been shown to accelerate between chemotherapy treatments. “Our results indicate that damage responses in benign cells… may directly contribute to enhanced tumor growth kinetics,” wrote the team. The researchers said they confirmed their findings with breast and ovarian cancer tumors.
Dr. Nelson describes the normal insanity/methods of chemotherapy saying, “In the laboratory we can ‘cure’ most any cancer simply by giving very high doses of toxic therapies to cancer cells in a petri dish. However, in people, these high doses would not only kill the cancer cells but also normal cells and the host.” Therefore, treatments for common solid tumors are given in smaller doses and in cycles, or intervals, to allow the normal cells to recover. This approach may not eradicate all of the tumor cells, and those that survive can evolve to become resistant to subsequent rounds of anti-cancer therapy.
What mainstream researchers are failing to find is that we can approach cancer treatment from a completely different and opposite angle to chemotherapy. Instead of trying to kill the cancer and harm the surrounding cells we imprison the cancer in a solid wall of healthy cells, thus that area being strengthened as opposed to being weakened by treatments. We create the conditions where we first limit the ability to grow and then send in some cruise missiles that directly target the cancer cells, choking the life out of them with waves of increased alkalinity and oxygen.