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Mechanobiology of Disease
Poster Abstracts
102
9-POS
Board 9
Topography Induces Differential Sensitivity on Cancer Cell Proliferation
Parthiv Kant Chaudhuri
1
, Catherine Qiurong Pan
1
, Boon Chuan Low
1,2
, Chwee Teck Lim
1,3
.
1
Mechanobiology Institute, National University of Singapore, SINGAPORE,
Singapore,
2
National University of Singapore, SINGAPORE, Singapore,
3
National University of
Singapore, SINGAPORE, Singapore.
Cancer is presently one of the topmost non-communicable diseases and the microenvironment
that surrounds the cancerous cells plays a critical role in determining the metastatic ability of the
malignant cells. During the progression of breast cancer, the extracellular matrix (ECM) fibers
that surrounds the cancer cells align themselves in a parallel orientation and this helps in the
migration of the tumor cells away from the primary tumor. Since cancer cells also possess
uncontrolled proliferation ability, here we questioned whether such changes in the ECM
topography during tumor progression could also affect the proliferation efficiency of the cancer
cells. To answer this question, we used micro fabrication tools to mimic such topographic
features
in-vitro
by fabricating microgratings of specific dimensions. We discovered the
existence of a Mechanically Induced Dormancy (MID) where the anisotropic topographical cues
provided by microgratings could reduce normal healthy cell proliferation; however, the cancer
cells could successfully overcome this mechanical barrier and continue uncontrolled
proliferation. Further research to understand the molecular mechanism of proliferation reduction
led to the identification of higher Rho-ROCK-Myosin based contractility in normal cells that
generates mechanical cues to prevent their proliferation. This study reveals a novel mechanism
by which normal cells could sense external mechanical cues and restrict their proliferation in a
microenvironment that promotes tumor progression.