More research presented today at AACR’s 101st annual meeting shed some light on the mind blowing complexity of cancer. At this morning’s plenary sessions, Alan Balmain of the University of California San Francisco showed how the simple model of cancer initiation leading to progression and metastasis was a vast oversimplification. Cancer cells, he says require help from otherwise normal stromal cells, blood vessels, and inflammatory cells. And while much of the research presented at this meeting has been about cataloguing mutations that are gained in cancer, he’s been trying to better understand the underlying genetic background that plays a role in intrinsic susceptibility to cancers.
It’s hard to pull such genes out from studies of humans, so he crossed two strains of mouse, one that is susceptible to cancer and one that is relatively resistant, essentially creating a heterogeneous population of offspring with variable susceptibility to cancer. On these mice he did gene expression analysis for different skin samples and tumor samples. This analytical approach helps to uncover genes that are working in concert to influence cancer susceptibility, thus exposing deeper networks of genes at play in the process that can have interlinked function. Mice that were susceptible to tumors, for example were enriched for expression of genes involved in determining an epidermal skin cell fate, as opposed to a sebaceous or follicle fate. Genes involved in mitosis were upregulated, wound healing genes were upregulated, and genes for reigning in the inflammatory response were upregulated.
Balmain went a bit more into depth on the inflammatory genes however. Generally inflammation is generally associated with increased cancer susceptibility, but anti-inflammatory drugs have different effects on the development of skin tumors. Sometimes increasing tumor spread and other times preventing against it. Balmain’s systems biology approach has indicated a number of genes related to controlling inflammation and shows how they could be related to cancer susceptibility in his mouse population. See a paper on it from last year, here. But it’s complex relationship. It’s times like this that I consider the Thermos: it keeps things hot and it keeps things cold. Whenever something seems to have an important job in biology like preventing cancer, it almost always does exactly the opposite with a subtle shift in context.