In metastasis cells from a primary tumor migrate to a distal organ site to colonize and proliferate. It is the leading cause of cancer related fatalities. Cancer cells experience a variety of mechanical forces in the extracellular matrix and blood stream during their migration. Cell membrane on which the mechanical forces are exerted possesses mechanical properties such as elasticity and stiffness and cells possess genes and proteins that are mechanosensitive.  A significant knowledge gap in the understanding of metastasis is the influence of extracellular mechanical stress through cell membrane mechanical properties and mechanosensitive genes and proteins. The central hypothesis of this research is that mechanical stress experienced by cancer cell membranes is transduced through the cellular structure to provide them metastatic character.  The research to substantiate the central hypothesis has been conducted along these lines employing normal and cancer prostate cell lines: (1) cell mechanical properties have been characterized by AFM, (2) expression levels of mechanosensitive membrane proteins without and with osmotic stress have been determined, (3) invasion through a membrane to mimic extracellular matrix have been studied, and (4) activation of cytoplasmic protein cSrc associated with the mechanosensitive membrane protein integrin in response to osmotic stress has been investigated with a cSrc protein probe with CFP-YFP FRET pair. Results of these studies indicate that mechanical properties of migrating cancer cells could have a significant influence on mechanotransduction and as a result on metastasis.  Significance ofresults these studies will be presented.

Role of extracellular mechanical stress in cancer metastasis

240th National Meeting (2010)

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