CSPG4 is stimulated by IL11 and promotes endometrial cancer growth

Lead researcher

Associate Professor Evdokia Dimitriadis

Main finding

Endometrial cancer occurs in the lining of the uterus and is the most common cancer of the female genital tract and the fourth most common cancer in women. We had already identified interleukin 11 (IL11) a cytokine present in the normal cycling endometrium, as a critical mediator of endometrial cancer. We have now also demonstrated in this study that Chondroitin sulfate proteoglycan (CSPG4), a cell surface proteoglycan is upregulated by IL11 in human endometrial epithelial cancer cells both in vitro and in vivo mouse endometrial cancer model. Functionally, the loss of CSPG4 in endometrial cancer cells reduced growth and movement in vitro. Our data suggests that elevations of CSPG4 expression/function could be pro-tumourigenic in women.

Centre

Centre for Reproductive Health

Research group

Embryo Implantation

Co-authors

Dr Amy Winship, Dr Michelle Van Sinderen, Ariella Heffernan-Marks

Journal and article title

Most surprising

This study is the first to identify and determine a functional role for CSPG4 in endometrial cancer.

Future implications

Further investigation of the role of CSPG4 in endometrial cancer pre-clinical cancer models could support our findings and determine the potential of targeting CSPG4 for clinical translation as a new treatment option for women with endometrial cancer

Disease/health impact

Endometrial Cancer

Other points of interest

Recently, we identified CSPG4 in the human placenta, showing that it localized to invasive and proliferative trophoblast subtypes of the placenta and the maternal uterine decidua. Furthermore, it was revealed that knockdown of CSPG4 stimulated HTR8/SVneo trophoblast cell line proliferation, but decreased migration. The data from this study highlights similar roles for CSPG4 in human trophoblast and endometrial cancer cell migration, but opposing regulation of proliferation, suggesting that the functional roles of CSPG4 in regulating cell cycle/growth in the uterine environment are cell-dependent

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