Wnt11 alters integrin and cadherin expression by ovarian cancer spheroids and inhibits tumorigenesis and metastasis

Exp Cell Res. 2018 Aug 1;369(1):90-104. doi: 10.1016/j.yexcr.2018.05.010. Epub 2018 May 16.

Abstract

The present study investigated the role of Wnt11 in multicellular tumor spheroid-like structures (MCTS) ovarian cancer cell proliferation, migration and invasion in vitro and in vivo tumorigenesis and metastasis in xenograft nude mice model. Moreover, samples from human serous ovarian cancer (SOC) were used to assess the association of Wnt11 with integrins and cadherins. The data showed that Wnt11 overexpressing SKOV-3 cells became more compact accompanied by increased expression of E-and N-cadherin and lower expression of EpCAM and CD44. The α5, β2, β3 and β6 integrin subunits expression levels were significantly reduced in Wnt11 overexpressing cells accompanied with significantly reduced disaggregation of Wnt11 overexpressing SKOV-3 MCTS on ECM components. Moreover, Wnt11 overexpressing SKOV-3 MCTS showed decreased migration, invasion as well as no tumor growth and metastasis in vivo. We found that Wnt11 significantly and negatively correlated with ITGB2, ITGB6, and EpCAM and positively with CDH-1 in high-grade SOC specimens. Our results suggest that Wnt11 impedes MCTS attachment to ECM components and therefore can affect ovarian cancer progression.

Keywords: Cadherin; Epithelial ovarian cancer; Integrin; Metastasis; Spheroids; Tumorigenesis; Wnt11.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Animals
  • Cadherins / genetics*
  • Carcinogenesis / genetics*
  • Carcinogenesis / pathology
  • Carcinoma, Ovarian Epithelial / genetics*
  • Carcinoma, Ovarian Epithelial / metabolism
  • Carcinoma, Ovarian Epithelial / pathology
  • Cell Adhesion / genetics
  • Down-Regulation / genetics
  • Extracellular Matrix / metabolism
  • Extracellular Matrix / pathology
  • Female
  • Gene Expression Regulation, Neoplastic
  • Humans
  • Integrins / genetics*
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Middle Aged
  • Neoplasm Metastasis
  • Ovarian Neoplasms / genetics*
  • Ovarian Neoplasms / metabolism
  • Ovarian Neoplasms / pathology
  • Spheroids, Cellular / metabolism*
  • Spheroids, Cellular / pathology
  • Tumor Cells, Cultured
  • Wnt Proteins / physiology*
  • Young Adult

Substances

  • Cadherins
  • Integrins
  • Wnt Proteins
  • Wnt11 protein, human