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Mar 23, 2011

Extracellular Matrix Tugging Augments Cancer Metastasis

  • The answer to what makes malignant tumors spread lies within the dense, fibrous matrix that surrounds cancer cells, according to a Wayne State University researcher. Karen A. Beningo, Ph.D., assistant professor of biology in WSU’s College of Liberal Arts and Sciences, found that the continuous restructuring of the extracellular matrix, which upholds the weight of a tumor, is one of the reasons highly invasive, malignant tumors are mechanically able to spread to other parts of the body.

    “This study has identified a novel physical parameter and a new conceptual framework in which to assess the process of invasion, not just of cancer cells but other invasive cell types as well,” remarks Dr. Beningo. Her study was published in PLoS ONE in a paper titled “Cancer Cell Invasion Is Enhanced by Applied Mechanical Stimulation.”

    The tumor microenvironment is rich in many cell types including highly contractile cells that are responsible for extensive remodeling and production of the dense extracellular matrix surrounding the cancerous tissue, Dr. Beningo explains. She set out to evaluate the role of mechanical forces produced by remodeling activities of cells in the tumor microenvironment in the invasion efficiency of metastatic cells.

    Dr. Beningo simulated the tugging and pulling forces by embedding magnetic microbeads in the collagen matrix of a 3-D, cell-based assay. She explains that this allowed her to examine the physical mechanisms without the complication of secreted biochemical factors.

    “Surprisingly, we found that cancer cells were two to four times more likely to invade if the matrix was magnetically stimulated than if the culture was not stimulated,” Dr. Beningo reports. The research also found that less invasive tumors were not as stimulated by the tugging and pulling forces of the extracellular matrix as highly invasive tumors.

    Moreover, the absence of fibronectin, a component of the extracellular matrix, and cofilin, a cellular protein, removed the tumor’s sensitivity to the mechanical stimulus. “We can conclusively state that fibronectin and cofilin are required for this mechanical response,” says Dr. Beningo.

    She is now working toward defining the mechanism of mechanically enhanced invasion and hopes to identify therapeutic targets.



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