Collective invasion of the basement membrane in breast cancer driven by forces from cell volume expansion and local contractility

Chang, J.; Saraswathibhatla, A.; Song, Z.; Varma, S.; Sanchez, C.; Srivastava, S.; Liu, K.; Bassik, M. C.; Marinkovich, M. P.; Hodgson, L.; Shenoy, V.; West, R. B.; Chaudhuri, O.

doi:10.1101/2022.07.28.501930

bioRxiv · 10.1101/2022.07.28.501930

Collective invasion of the basement membrane in breast cancer driven by forces from cell volume expansion and local contractility

Chang, J.·Saraswathibhatla, A.·Song, Z.·Varma, S.·Sanchez, C.·Srivastava, S.·Liu, K.·Bassik, M. C.·Marinkovich, M. P.·Hodgson, L.·Shenoy, V.·West, R. B.·Chaudhuri, O.

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Abstract

Breast cancer becomes invasive when carcinoma cells collectively invade through the basement membrane (BM), a nanoporous layer of matrix that physically separates the primary tumor from the stroma, in a first step towards metastasis. Single cells can invade through nanoporous three-dimensional (3D) matrices via protease-mediated degradation or, when the matrix exhibits sufficient mechanical plasticity, force-mediated widening of pores. However, how cells invade collectively through physiological BM layers in cancer remains unclear. Here, we developed a 3D in vitro model of collective invasion of the BM during breast cancer. We show that cells utilize both proteases and forces to breach the BM. Forces are generated from a combination of global cell volume expansion that stretch the BM with local contractile forces that act in the plane of the BM to breach it, allowing invasion. These results uncover a mechanism by which cells collectively interact to overcome a critical barrier to metastasis.

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Chang, J., Saraswathibhatla, A., Song, Z., Varma, S., Sanchez, C., Srivastava, S., Liu, K., Bassik, M. C., Marinkovich, M. P., Hodgson, L., Shenoy, V., West, R. B., Chaudhuri, O.. 2022-07-31. Collective invasion of the basement membrane in breast cancer driven by forces from cell volume expansion and local contractility. https://doi.org/10.1101/2022.07.28.501930

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