title: Chondroitin sulfate proteoglycan protein is stimulated by interleukin 11 and promotes endometrial epithelial cancer cell proliferation and migration.
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.
authors.affiliation: Centre for Reproductive Health, The Hudson Institute of Medical Research, Clayton, 3168 VIC, Australia.
authors.forename: Amy
authors.initials: A
authors.lastname: Winship
authors.affiliation: Centre for Reproductive Health, The Hudson Institute of Medical Research, Clayton, 3168 VIC, Australia.
authors.forename: Michelle
authors.initials: M
authors.lastname: Van Sinderen
authors.affiliation: Centre for Reproductive Health, The Hudson Institute of Medical Research, Clayton, 3168 VIC, Australia.
authors.forename: Ariella
authors.initials: A
authors.lastname: Heffernan-Marks
authors.affiliation: Centre for Reproductive Health, The Hudson Institute of Medical Research, Clayton, 3168 VIC, Australia.
authors.forename: Eva
authors.initials: E
authors.lastname: Dimitriadis
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002465:Cell Movement / Q000235:genetics; D049109:Cell Proliferation / Q000235:genetics; D011508:Chondroitin Sulfate Proteoglycans / Q000235:genetics / Q000378:metabolism*; D016889:Endometrial Neoplasms / Q000473:pathology*; D004717:Endometrium / Q000166:cytology / Q000473:pathology*; D058750:Epithelial-Mesenchymal Transition / Q000235:genetics*; D005260:Female; D006801:Humans; D017370:Interleukin-11 / Q000378:metabolism*; D008565:Membrane Proteins / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D008807:Mice, Inbred BALB C; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D034622:RNA Interference; D012333:RNA, Messenger / Q000096:biosynthesis; D034741:RNA, Small Interfering / Q000235:genetics; D000071250:Snail Family Transcription Factors / Q000235:genetics / Q000378:metabolism; D014183:Transplantation, Heterologous; D000099216:Chondroitin Sulfate Proteoglycan 4
chemical_list: D011508:Chondroitin Sulfate Proteoglycans; D017370:Interleukin-11; D008565:Membrane Proteins; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D000071250:Snail Family Transcription Factors; C101390:CSPG4 protein, human; D000099216:Chondroitin Sulfate Proteoglycan 4; C508611:IL11 protein, human