title: Breast cancer cells mechanosensing in engineered matrices: Correlation with aggressive phenotype.
abstract: The pathogenesis of cancer is often driven by the modulation of the tumor microenvironment. Recent reports have highlighted that the progressive stiffening of tumor matrix is crucial for malignant transformation. Though extensive work has been done analyzing the mechanotransductive signals involved in tumor progression, it is still not clear whether the stiffness induced changes in cancer cell behavior is conserved across the invasive/aggressive phenotype of cells. Here, we used synthetic hydrogel based cell culture platform to correlate the aggressive potential of the breast cancer cells to the responses to matrix stiffness. The cellular functions such as proliferation, migration, and angiogenic capability were characterized. We report that the proliferation and motility of the highly aggressive cell line MDA-MB-231 increased with increase in matrix rigidity. We also demonstrated for the first time that the change in matrix stiffness stimulated the angiogenic activity of these cells as manifested from enhanced expression of vascular endothelial growth factor (VEGF). Inhibition of actomyosin contractility attenuated proliferation of MDA-MB-231 cells on stiff matrices while promoted the growth on soft gels. In addition, the release of VEGF was reduced upon inhibition of contractility. The less and non-aggressive breast cancer cells, SKBr3 and MCF-7 respectively displayed less dependency on matrix stiffness.
authors.affiliation: Bioengineering Program, Department of Mechanical Engineering, University of Michigan, Dearborn, 4901 Evergreen Road, Dearborn, MI 48128, USA.
authors.forename: Ji
authors.initials: J
authors.lastname: Li
authors.affiliation: Bioengineering Program, Department of Mechanical Engineering, University of Michigan, Dearborn, 4901 Evergreen Road, Dearborn, MI 48128, USA.
authors.forename: Yang
authors.initials: Y
authors.lastname: Wu
authors.affiliation: Bioengineering Program, Department of Mechanical Engineering, University of Michigan, Dearborn, 4901 Evergreen Road, Dearborn, MI 48128, USA.
authors.forename: Nicholas
authors.initials: N
authors.lastname: Schimmel
authors.affiliation: Bioengineering Program, Department of Mechanical Engineering, University of Michigan, Dearborn, 4901 Evergreen Road, Dearborn, MI 48128, USA.
authors.forename: Mohammad Ali
authors.initials: MA
authors.lastname: Al-Ameen
authors.affiliation: Bioengineering Program, Department of Mechanical Engineering, University of Michigan, Dearborn, 4901 Evergreen Road, Dearborn, MI 48128, USA. Electronic address: gargi@umich.edu.
authors.forename: Gargi
authors.initials: G
authors.lastname: Ghosh
mesh_terms: D001943:Breast Neoplasms / Q000473:pathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D005109:Extracellular Matrix / Q000737:chemistry*; D006801:Humans; D040542:Mechanotransduction, Cellular; D009389:Neovascularization, Pathologic; D010641:Phenotype; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A
keywords: Actomyosin tension; Aggressive phenotype; Angiogenic activity; Cancer; Matrix stiffness