Tropomyosin-related kinase B (TrkB) full-length isoform is related to advanced-stage clear cell ovarian cancer (CCOC)

Objective: Tropomyosin-related kinase B receptor (TrkB) is a receptor tyrosine kinase (RTK) that regulates the follicular growth and oocyte survival in the ovaries and is overexpressed in various cancers. Previously, we reported the increased expression of the TrkB isoform with tyrosine kinase (TrkB-TK) in Japanese clear cell ovarian cancer (CCOC) cases. In this study, we quantified TrkB isoform in French CCOC clinical samples and ovarian cancer cell lines to examine that the increased TrkB-TK expression was a common CCOC characteristics and to examine whether TrkB-TK associates with the resistance to cisplatin. Methods: The mRNA level of TrkB isoforms in twenty French CCOC cases and seventeen ovarian cancer cell lines involving twelve CCOC were quantified by real-time PCR. The expression of TrkB protein in twelve of these French CCOC samples were examined by immunohistochemistry (IHC). Four CCOC cell lines which expressed TrkB mRNA were selected, and in vitro cell viability assay was performed using a pan-Trk inhibitor K252a and cisplatin. Results: TrkB mRNA was expressed in all French CCOC cases and TrkB-TK was expressed at 70%. In advanced cases, TrkB-TK tended to increase. In addition, cell lines highly expressing TrkB-TK tended to be more cisplatin-sensitive under K252a treatment. Discussion: TrkB may be expressed in most of CCOC tissues. The TrkB-TK has a possibility to be involved in CCOC malignancy. Treatment with a pan-Trk inhibitor might be an adjuvant therapeutic strategy for patients with TrkB-TK expression including CCOC. Conclusion: TrkB was expressed in all French CCOC cases examined. High TrkB-TK expression was observed in advanced cases. TrkB-TK expressing CCOC cell lines tended to be more cisplatin-sensitive under K252a treatment.

Tropomyosin-related kinase B (TrkB); Brain-derived neurotrophic factor (BDNF); Clear cell ovarian cancer (CCOC); Splicing variants; Cisplatin; Pan-Trk inhibitor

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