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SHH and IHH protein expression in high-grade serous ovarian carcinomas

Background: High-grade serous ovarian carcinomas (HGSCs) are the most common and lethal type of all epithelial ovarian cancers. The aberrant activation of several signaling pathways, including the Hedgehog (HH) signaling pathway, has been observed in ovarian cancer. HH signaling is activated by HH ligands, Sonic Hedgehog (SHH), Indian Hedgehog (IHH), and Desert Hedgehog (DHH), which inhibit the transmembrane protein PTCH. The role of the Hh signaling pathway in ovarian cancer has not been sufficiently investigated. In the current study, we explored the expression of SHH and IHH proteins in a cohort of serous ovarian carcinomas and cell lines. Design: Formalin-fixed paraffin-embedded (FFPE) samples of 37 HGSCs were used for this study, while normal ovarian (n=20) and fallopian tube tissue samples (n=10) served as controls. HGSC cell lines, OVCAR5, OVCAR8, and OVSHAO, and control cell line, normal fallopian tube non ciliated epithelium cell line FNE1, were also used in the study. SHH and IHH expression were analyzed using immunohistochemistry in tissue samples and by immunofluorescence in cell lines. Results: SHH and IHH protein expression were significantly higher in HGSCs compared with both healthy ovarian surface epithelium (p<0.001 and p<0.001, respectively) and healthy fallopian tube epithelium (p=0.04 and p<0.001, respectively). Similarly, SHH and IHH protein expression was significantly higher in HGSC cell lines, OVCAR5, OVCAR8, and OVSAHO compared with normal fallopian tube non-ciliated epithelium cell line, FNE1. Conclusions: Our data indicate that HH ligands SHH and IHH may play an active role in the molecular pathogenesis of high-grade serous ovarian carcinomas. Increased SHH and IHH protein expression in HGSC samples and cell lines indicate that the tumor promoter role of these ligands can potentially be achieved through autocrine SHH and IHH signaling. Therefore, these HH ligands might serve as potential therapeutic targets for HGSCs. Further studies should confirm these findings and their clinical relevance.

high-grade serous ovarian carcinoma ; Hedgehog signaling pathway ; SHH ; IHH ; ovarian cancer cell lines

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