Imatinib sensitizes endometrial cancer cells to cisplatin by targeting CD117-positive growth-competent cells

Cancer Letters
Xiuzhi ZhangHiroshi Fujiwara

Abstract

The use of molecular target therapy has not been established for endometrial cancer. The present study investigated the potential therapeutic strategy of targeting CD117-positive cancer cells as a novel molecular target therapy. FACS-sorted CD117(+) cells isolated from endometrial cancer cell lines (Ishikawa or MFE280 cells) exhibited higher proliferative capacity in vitro and colony forming activity on soft agar, and decreased sensitivity to cisplatin, compared to CD117(-) cells. Immunohistochemical analyses with surgical specimens of endometrial cancers showed that high CD117 expression was tightly linked to advanced FIGO stages, myometrial invasion and histological grade, and was significantly associated with poor overall survival and relapse-free survival (Kaplan-Meier analysis; p<0.001, log-rank test). The Cox-regression hazard model identified high CD117 expression to be an independent prognostic factor for survival (p<0.05). In vitro assay confirmed that stem cell factor (SCF), a ligand of CD117, was produced specifically in CD117(+) cells of endometrial cancer, and the colony-forming activity were abrogated by adding anti-SCF antibody, indicating an SCF-dependent growth property. Imatinib was confirmed to selectively ta...Continue Reading

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Citations

Dec 25, 2015·Human Mutation·Min ZhaoTracy A O'Mara
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Jun 28, 2016·Oncotarget·Ruixia Huang, Einar K Rofstad
Aug 8, 2021·International Journal of Molecular Sciences·Tomohiko FukudaCarl-Henrik Heldin

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