UC San Diego

Cancer has classically been understood as the malignant growth of cells caused by the gradual acquisition of mutations that allow these cells to avoid normal checks on cell growth, division, and death. However, new findings are showing that the tumor microenvironment also plays a crucial role in the promotion of cancer growth by regulating factors such as angiogenesis, the immune response, and the extracellular matrix. One of the key mediators of these factors is the fibroblast. In the presence of tumors, fibroblasts gain an activated phenotype, which allows them to stimulate angiogenesis, the immune response, and ECM remodeling. In addition, many carcinomas express the transcription factor Snail, and our lab has shown that noncancerous Snail transgenic keratinocytes are sufficient to activate dermal fibroblasts. Considering these factors, it is possible that Snail-expressing cancer cells cause the activation of surrounding fibroblasts, which allows the fibroblast to create a microenvironment conducive to tumor growth. To test this hypothesis, various cancer cells were screened for Snail expression by RT-PCR, Western blot, and immunofluorescence. Conditioned media from cell cultures was then added to fibroblasts, which were assayed for activation by their ability to contract collagen, proliferate, and express the activation marker [alpha]-SMA to test whether fibroblast activation could be correlated with Snail expression. Snail expression could not be correlated with collagen contraction, but it could be correlated with proliferation, suggesting that Snail expression could be a factor in activation but not be entirely sufficient for total activation