Breast cancer cells grown in dense tissues promote aggressive cancers, a new study from Vanderbilt-Ingram Cancer Centre has found.
The research team found that breast cancer cells grown in dense, rigid surroundings increased their invasive activities. Women with increased breast density on mammograms have an increased risk for both developing breast cancer and having breast cancers with invasive characteristics.
"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.
The team led by Weaver focussed their study over invadopodia - the finger-like protrusions that a cancer cell uses to drill holes in the extracellular matrix. 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," said Weaver.
They found that breast cancer cells cultured on a denser - and thus, more rigid - matrix had a greater number of active invadopodia than breast cancer cells cultured on a less dense matrix.
"We thought that more ''stuff'' for the cells to get through was going to make it harder, so we expected to see less matrix degradation, but instead we found this interesting effect where cells actually sense the rigidity and degrade more," said Weaver.
The investigators also implicated the activities of two signalling proteins called FAK and p130Cas in the rigidity-induced invadopodia activity. These signaling proteins were present in an activated state in the invadopodia, suggesting that they are important players in this response and may represent targets for anti-invasive therapies.
She said that it''s exciting to find a cellular mechanism that could explain why denser breast tissue is correlated with more aggressive tumours and a poorer prognosis for patients.
"The idea that tissue rigidity leads to a more aggressive phenotype had been out there for a while but it hadn''t actually been tied to matrix degradation, which is thought to be important for metastasis and spread of cells through the body," she said.
The report appears in Sept. 9 issue of Current Biology.