Chondroitin sulfate proteoglycan protein is stimulated by interleukin 11 and promotes endometrial epithelial cancer cell proliferation and migration

Amy Winship, Michelle Van Sinderen, Ariella Heffernan-Marks, Eva Dimitriadis

Research output: Contribution to journalArticleResearchpeer-review

7 Citations (Scopus)

Abstract

Endometrial cancer is the most common gynecological cancer. We identified interleukin 11 (IL11) as a critical mediator of endometrial tumourigenesis and demonstrated that IL11 regulates chondroitin sulfate proteoglycan (CSPG4) in human placental trophoblasts. CSPG4 is a cell membrane protein overexpressed in numerous human cancers, although its role in endometrial cancer has not been investigated. We examined CSPG4 expression and localization in primary human type I endometrioid grade (G) 1-3 tumours by qPCR and immunohistochemistry and determined whether IL11 stimulated CSPG4. IL11 upregulated CSPG4 mRNA in HEC1A (G2-derived endometrial epithelial cancer cell line) cells. IL11 administration to BALB/c nude mice enhanced HEC1A xenograft tumour growth and increased CSPG4 protein in tumours. CSPG4 mRNA was unchanged between human G1-3 endometrial cancer and control tissues. CSPG4 protein levels were elevated in the epithelium of G2 and G3 endometrial cancer and in the tumour-Associated stroma of G3 tumour tissues compared to proliferative phase or post-menopausal endometrium. CSPG4 knockdown by siRNA reduced HEC1A proliferation and migration in vitro and reduced gene expression of the key epithelial-To-mesenchymal transition (EMT) regulator SNAIL. Our data suggest that CSPG4 inhibition may impair endometrial cancer progression by reducing cancer cell proliferation, migration and potentially EMT.

Original languageEnglish
Pages (from-to)798-804
Number of pages7
JournalInternational Journal of Oncology
Volume50
Issue number3
DOIs
Publication statusPublished - 1 Mar 2017

Keywords

  • Endometrioid
  • Endometrium
  • Membrane

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