Extracellular vesicles derived from ascitic fluid enhance growth and migration of ovarian cancer cells

Sci Rep. 2021 Apr 28;11(1):9149. doi: 10.1038/s41598-021-88163-1.

Abstract

Ovarian cancer is associated with a high mortality rate due to diagnosis at advanced stages. Dissemination often occurs intraperitoneally within the ascites fluid. The microenvironment can support dissemination through several mechanisms. One potential ascites factor which may mediate dissemination are EVs or extracellular vesicles that can carry information in the form of miRNAs, proteins, lipids, and act as mediators of cellular communication. We present our observations on EVs isolated from ascitic supernatants from patients diagnosed with high grade serous ovarian carcinoma in augmenting motility, growth, and migration towards omental fat. MicroRNA profiling of EVs from malignant ascitic supernatant demonstrates high expression of miR 200c-3p, miR18a-5p, miR1246, and miR1290 and low expression of miR 100- 5p as compared to EVs isolated from benign ascitic supernatant. The migration of ovarian cancer spheroids towards omental fat is enhanced in the presence of malignant ascitic EVs. Gene expression of these cells showed increased expression of ZBED2, ZBTB20, ABCC3, UHMK1, and low expression of Transgelin and MARCKS. We present evidence that ovarian ascitic EVs increase the growth of ovarian cancer spheroids through miRNAs.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aged
  • Ascitic Fluid / metabolism*
  • Cell Line, Tumor
  • Cell Movement / drug effects
  • Cell Proliferation / drug effects
  • Down-Regulation / drug effects
  • Extracellular Vesicles / metabolism*
  • Female
  • Humans
  • MicroRNAs / metabolism
  • MicroRNAs / pharmacology
  • Microfilament Proteins / genetics
  • Microfilament Proteins / metabolism
  • Middle Aged
  • Multidrug Resistance-Associated Proteins / genetics
  • Multidrug Resistance-Associated Proteins / metabolism
  • Muscle Proteins / genetics
  • Muscle Proteins / metabolism
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology*
  • Spheroids, Cellular / cytology
  • Spheroids, Cellular / metabolism
  • Tumor Microenvironment
  • Up-Regulation / drug effects

Substances

  • MicroRNAs
  • Microfilament Proteins
  • Multidrug Resistance-Associated Proteins
  • Muscle Proteins
  • transgelin
  • multidrug resistance-associated protein 3