Dense tissue promotes aggressive cancers( New research may explain why breast ...)

New research may explain why breast cancer tends to be more aggressive in women with denser breast tissue.

Breast cancer cells grown in dense, rigid surroundings step up their invasive activities, Vanderbilt-Ingram Cancer Center investigators report in the Sept. 9 issue of Current Biology.

The findings suggest a cellular mechanism for the correlation between human breast tissue density and tumor aggressiveness. Women with increased breast density on mammograms have an increased risk for both developing breast cancer and having breast cancers with invasive characteristics.

This connection between breast density and cancer aggressiveness has begged the question of which comes first. Is the tissue denser because the tumor is more aggressive (and recruits cells that "lay down" more matrix), or is the tumor more aggressive because the tissue is denser?

"Our study shows that if you have a dense, rigid matrix, the cells will be more aggressive and invasive; it's a direct effect," said Alissa Weaver, M.D., Ph.D., assistant professor of Cancer Biology and lead author of the study.

Weaver and colleagues were interested in invadopodia the finger-like protrusions that a cancer cell uses to drill holes in the extracellular matrix (matrix-degrading enzymes are associated with invadopodia). These structures are believed to be important for cancer invasion.

"If you have enough invadopodia, over time they'll make large holes that cells can move through to invade and metastasize," Weaver said.

Despite the intimate connection between invadopodia and the matrix, very little was known about what role the matrix might play in regulating invadopodia function. Weaver and colleagues started probing this question as part of computational math modeling project through the Vanderbilt Integrative Cancer Biology Center.

They were surprised to find that breast cancer cells cultured on a denser and thus, more rigid matrix had a greater number of activ
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