Mutations alone are not enough to Cause Cancer

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 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 contributes to how cancer has occurred.

Cancer involves an interaction between rogue cells and surrounding tissue. This is the clear message of 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 macroenvironment 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.[1] 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, 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. 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.

[1] Putting tumours in context; Bissell MJRadisky D.; Nat Rev Cancer. 2001 Oct;1(1):46-54.;