Deciphering Biophysical Modulation in Ovarian Cancer Cells

• Published in: Cell biochemistry and biophysics 2021-06, Vol.79 (2), p.375-386
• Main Authors: Sarwar, Makhdoom, Sykes, Peter H., Chitcholtan, Kenny, Evans, John J.
• Format: Article
• Language: English
• Subjects: Adhesion; Biochemistry; Biological and Medical Physics; Biomedical and Life Sciences; Biophysics; Biotechnology; Cancer; Cell adhesion; Cell Adhesion - physiology; Cell Biology; Cell growth; Cell interactions; Cell Line, Tumor; Cell proliferation; Cell Proliferation - drug effects; CSK Tyrosine-Protein Kinase - antagonists & inhibitors; CSK Tyrosine-Protein Kinase - metabolism; Down-Regulation - drug effects; Female; Focal Adhesion Kinase 1 - antagonists & inhibitors; Focal Adhesion Kinase 1 - metabolism; Humans; Life Sciences; MAP kinase; MAP Kinase Kinase Kinases - metabolism; Mechanotransduction; Mechanotransduction, Cellular; Modulation; Original Paper; Ovarian cancer; Ovarian Neoplasms - metabolism; Ovarian Neoplasms - pathology; Pharmacology/Toxicology; Protein Kinase Inhibitors - pharmacology; rho-Associated Kinases - metabolism; rhoA GTP-Binding Protein - metabolism; Signal transduction; Signal Transduction - physiology; Signaling; Src protein; Substrates; Topography; Tumor Microenvironment; Tumors
• ISSN: 1085-9195; 1559-0283
• DOI: 10.1007/s12013-020-00964-9

It has been long known that the oncogenic extracellular environment plays an indispensable role in developing and nurturing cancer cell progression and in resistance to standard treatments. However, by how much the biophysical components of tumour extracellular environment contribute to these processes is uncertain. In particular, the topographic environment is scarcely explored. The biophysical modulation of cell behaviour is primarily facilitated through mechanotransduction-associated mechanisms, including focal adhesion and Rho/ROCK signalling. Dysregulation of these pathways is commonly observed in ovarian cancer and, therefore, biophysical modulation of these mechanisms may be of great importance to ovarian cancer development and progression. In this work, aspects of the biophysical environment were explored using a bioimprinting technique. The study showed that topography-mediated substrate sensing delayed cell attachment, however, cell–cell interactions overrode the effect of topography in some cell lines, such as OVCAR-5. Also, 3D topographical cues were shown to modulate the inhibition of focal adhesion and Rho signalling, which resulted in higher MAPK activity in cells on the bioimprints. It was revealed that c-Src is vital to the biophysical modulation of cell proliferation and inhibition of c-Src could downregulate biophysically modulated MAPK activity. This study provides evidence that the biophysical extracellular environment affects key intracellular mechanisms associated with tumourigenicity in ovarian cancer cells. Highlights Substrate cell-like topography regulates cell attachment in ovarian cancer cells. Biophysical cues influence sensitivity to inhibition of focal adhesion and Rho signalling. Rho regulates growth through MAPK in a cell line dependent manner. Src is vital to the biophysical modulation of cell growth in ovarian cancer cells.