UCSF studies illuminate possible new landscape for targeting cancer

Dual UCSF findings dramatize what scientists have just begun to recognize: While so-called oncogenic cells drive the development of cancerous tumors, other, seemingly innocent cells -- inflammatory cells - within emerging tumors can influence the fate of tumors, their aggression and their response to therapy.

The findings, both reported in recent publications, suggest that blocking the action of these 'innocent' cells - or the factors they release - may interrupt the progression of cancerous tumors at early stages of development, the researchers say.

"Tumor biology has historically focused on the cells that contain oncogenic or tumor-suppressor gene mutations. But the combined implication of our two studies suggests that we need to look beyond the mutated tumor cells and into their micro-environment, to take into account the regulation of inflammatory cells," says the lead author of one study, published in Cell, Lisa Coussens, PhD, assistant professor of pathology and a member of the UCSF Comprehensive Cancer Center.

In the Cell study, the researchers report that an enzyme known as matrix metalloproteinase-9 (MMP-9) significantly influences the progression of cancer development in mice engineered to express oncogenes, or tumor-causing genes, that predispose animals to develop squamous cell carcinomas, a common skin cancer in humans. Moreover, the researchers demonstrate that the primary source of the enzyme is not the oncogenic epithelial cells that drive the cancer, but immune inflammatory cells within the tumor's developing mass.

In the other study, published in Nature Cell Biology, the researchers demonstrate that the same enzyme is a key component of the "switch" that initiates angiogenesis, the growth of blood vessels, in mice genetically engineered to develop carcinomas of the pancreatic islets. Angiogenesis supplies emerging tumors with the nutrients and oxygen that are essential for fueling their progressi

Contact: Jennifer O'Brien
University of California - San Francisco

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