In this latest study, Groves and his colleagues worked with mammary epithelial cells from a library of 26 model human breast cancer cell lines that have been well-characterized by co-author Gray and his research groups at Berkeley Lab and UC San Francisco.

Says co-author Nair, "Gray's research has demonstrated that this library substantially reproduces the genomic abnormalities and drug responsiveness of primary breast cancer tumor cells from patients, and constitutes the most comprehensive system for the study of the various aberrations responsible for human breast cancer."

To test the sensitivity of the EphA2/ephrin-A1 signaling complex to mechanical forces, Groves and his group patterned their silica substrates with chromium metal lines that were 10 nanometers in height and 100 nanometers wide. These metal lines acted as diffusion barriers that impeded the lateral mobility of the EphA2/ephrin-A1 complexes in the synthetic membrane. The movement and spatial organization of the complexes were subsequently tracked through a combination of Total Internal Reflection Fluorescence (TIRF), reflection interference and epifluorescence imaging techniques.

"Without the barriers, the clusters of EphA2/ephrin-A1 signaling complexes were transported to the center of the cell-supported membrane junction, but with the barriers in place, there was an accumulation of clusters at the barrier boundaries," Groves says. "This resulted in a spatial reorganization that altered the cell's biochemical behavior."

Quantitative analysis of these changes to the spatial organization of the EphA2/ephrin-A1 signaling complexes across the library of breast cancer cell lines revealed a strong correlation with the potential for metastasis. Since the patterned metal lines in the silica substrate are analogous to the stiffness, texture and other elastic and mechanical properties of tissue, as well as to internal structures within the cell membrane, the results of this study point to intriguing new possibilities for breast and other cancer therapies.

"It's possible that the force-sensing process itself could provide a target for therapeutic intervention," says Groves. "We're also excited about finding targets for which there may be drugs that have already been developed but are now being used to treat diseases other than cancer. Given the sensitivity to mechanical forces displayed by the EphA2/ephrin-A1 signaling complexes, it is possible these existing drugs could be redirected to the treatment of cancer."

Source: DOE/Lawrence Berkeley National Laboratory