Overexpression of human sperm protein 17 increases migration and decreases the chemosensitivity of human epithelial ovarian cancer cells

Abstract

BackgroundMost deaths from ovarian cancer are due to metastases that are resistant to conventional therapies. But the factors that regulate the metastatic process and chemoresistance of ovarian cancer are poorly understood. In the current study, we investigated the aberrant expression of human sperm protein 17 (HSp17) in human epithelial ovarian cancer cells and tried to analyze its influences on the cell behaviors like migration and chemoresistance.MethodsImmunohistochemistry and immunocytochemistry were used to identify HSp17 in paraffin embedded ovarian malignant tumor specimens and peritoneal metastatic malignant cells. Then we examined the effect of HSp17 overexpression on the proliferation, migration, and chemoresistance of ovarian cancer cells to carboplatin and cisplatin in a human ovarian carcinoma cell line, HO8910.ResultsWe found that HSp17 was aberrantly expressed in 43% (30/70) of the patients with primary epithelial ovarian carcinomas, and in all of the metastatic cancer cells of ascites from 8 patients. The Sp17 expression was also detected in the metastatic lesions the same as in ovarian lesions. None of the 7 non-epithelial tumors primarily developed in the ovaries was immunopositive for HSp17. Overexpression of HSp17 increased the migration but decreased the chemosensitivity of ovarian carcinoma cells to carboplatin and cisplatin.ConclusionHSp17 is aberrantly expressed in a significant proportion of epithelial ovarian carcinomas. Our results strongly suggest that HSp17 plays a role in metastatic disease and resistance of epithelial ovarian carcinoma to chemotherapy.

Increased levels of sperm protein 17 mRNA and circulating antibodies in periampullary carcinoma patients

“…Liggins et al reported that Sp17 expression was observed at higher frequencies in cell lines derived from more aggressive lymphoma subtypes [24]. Sp17 expression has also been shown to increase the migration and diminish the chemosensitivity of ovarian carcinoma cells to carboplatin and cisplatin [21]. Likewise, Kausar et al suggested that Sp17 could be used as a novel marker for predicting cisplatin response in esophageal squamous cell carcinoma [25].…”

Cancer Testis Antigen, Ropporin, Is a Potential Target for Multiple Myeloma Immunotherapy

“…However, as under physiologic conditions, ropporin has been shown to form a complex with rhophilin in sperm flagella 27 and rhophilin in turn regulates cell-substrate adhesion, motility, and cytokinesis, 34,35 we speculate that ropporin could regulate similar functions in MM cells, providing tumor cells with a selective growth and drug-resistance advantage, as has been shown in different contexts for other CTA, including MAGE [36][37][38] and Sp17. 39,40 Elucidation of ropporin-mediated activities in MM cells will be the goal of future studies, aiming to evaluate ropporin as a pharmacological or immunotherapeutic target in MM.…”

Sperm Protein 17: Clinical Relevance of a Cancer/Testis Antigen, from Contraception to Cancer Immunotherapy, and Beyond

“…Suppression of SP17 mRNA expression in human clear cell OC cell lines enhanced tumor cell sensitivity to paclitaxel, without directly influencing cell viability or growth [54]. Conversely, SP17 over-expression in the OC cell line HO8910 resulted in increased resistance to cisplatin and carboplatin and in a 2.3-fold increment in migratory ability [47]. Functional studies on SP17 roles and signals in cancer cells still need further and accurate investigations.…”

“…More recently, the studies on SP17 focused mainly on its functional significance in cancer cells. In 2009, Zeng and co-workers found that SP17 increased the migration potential and drug resistance in human epithelial OC cells [47], while in 2010 Kausar and colleagues reported that SP17 was involved in esophageal squamous cancer cell lines resistance to cisplatin [48]. In 2010, the first pre-clinical validation of SP17-targeted vaccine for ovarian cancer immunotherapy was reported in murine model of advanced disease [49].…”