May 10, 2018

The mechanical microenvironment regulates ovarian cancer cell morphology, migration, and spheroid disaggregation

Scientific Reports
Andrew J McKenzieAlan K Howe

Abstract

There is growing appreciation of the importance of the mechanical properties of the tumor microenvironment on disease progression. However, the role of extracellular matrix (ECM) stiffness and cellular mechanotransduction in epithelial ovarian cancer (EOC) is largely unknown. Here, we investigated the effect of substrate rigidity on various aspects of SKOV3 human EOC cell morphology and migration. Young's modulus values of normal mouse peritoneum, a principal target tissue for EOC metastasis, were determined by atomic force microscopy (AFM) and hydrogels were fabricated to mimic these values. We find that cell spreading, focal adhesion formation, myosin light chain phosphorylation, and cellular traction forces all increase on stiffer matrices. Substrate rigidity also positively regulates random cell migration and, importantly, directional increases in matrix tension promote SKOV3 cell durotaxis. Matrix rigidity also promotes nuclear translocation of YAP1, an oncogenic transcription factor associated with aggressive metastatic EOC. Furthermore, disaggregation of multicellular EOC spheroids, a behavior associated with dissemination and metastasis, is enhanced by matrix stiffness through a mechanotransduction pathway involving ROC...Continue Reading

  • References117
  • Citations18
  • References117
  • Citations18

Citations

Mentioned in this Paper

Muscle Rigidity
Biochemical Pathway
Extracellular Matrix Constituent Secretion
Epithelial Ovarian Cancer
Protein Phosphorylation
Actomyosin Location
YY1AP1
Microscopy, Atomic Force
Ovarian Carcinoma
Human Cell Line

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