Oncogene S100A10 May Play Role in Progression of Ovarian Cancer

Oncogene S100A10 expression can be used as a predictive marker in the prognosis of ovarian cancer and may affect cell sensitivity to carboplatin, according to study findings published in the Journal of Ovarian Research.¹

“A better understanding of the pathways underlying tumor progression and chemoresistance might aid in the design of more effective treatment strategies in ovarian cancer,” the researchers wrote.

In this analysis of expression levels in tissues of S100A10 in 138 cases of ovarian cancer by immunohistochemistry, the results showed that increased expression of S100A10 was associated with carboplatin resistance (P < .001), tumor grade (P = .048), and a poorer prognosis (P = .0053).

Functional analyses demonstrated that S100A10 suppression significantly suppressed ovarian cancer cell proliferation, colony formation, cell migration and invasion, remarkably increased carboplatin-induced apoptosis in SKOV3 and A2780 cells, and inhibited tumor growth in vivo, according to the study. Downregulation of S100A10 expression could inhibit cell proliferation and enhance ovarian cancer cell sensitivity to carboplatin, possibly involving the regulation of cleaved-Caspase3 and cleaved-PARP.

“Elucidating the mechanisms involved in the progression and chemotherapy resistance of ovarian cancer is crucial for the discovery of novel molecular prognostic indicators and new therapeutic tests,” the researchers wrote.

Ovarian cancer is the most lethal gynecological malignancy with a 5-year survival rate of only about 46%, according to a 2018 article in the International Journal of Molecular Sciences. The poor survival rate can be attributed to the fact that ovarian cancer has non-specific symptoms and as a result is often diagnosed at stage III or IV. High recurrence rates following treatment and subsequent chemotherapy resistance is another reason.²

Abnormal expression of S100 proteins has been implicated in cancer, autoimmune diseases, and chronic inflammatory disorders. The association of S100A10 with clinicopathological characteristics in ovarian cancer and its biological functions have not yet been clarified.

Normal ovarian epithelium tissues were difficult to obtain; therefore, researchers could not assess the role of the translocation of S100A10 on its biological function.

A xenograft study could better reveal the association between the expression level of S100A10 and carboplatin sensitivity, according to the researchers. A xenograft study to investigate the sensitivity of SKOV3 cells to carboplatin will be considered in further studies. Additionally, the mechanisms of S100A10 involvement in carboplatin resistance are still unknown. Further studies are required to fully elucidate the molecular mechanisms through which S100A10 acts as a potential biomarker of the response to carboplatin in ovarian cancer.

S100A10, also known as p11 or annexin A2 light chain, is expressed ubiquitously in the majority of cells and plays a major role in fibrinolysis, wound healing, and angiogenesis. Recent studies have shown that S100A10 is important in regulating other physiological processes, including immune cell function, reproduction, neural cell function, and heart function.

References:
1. Wang L, Yan W, Li X, et al. S100A10 silencing suppresses proliferation, migration and invasion of ovarian cancer cells and enhances sensitivity to carboplatin. Journal of Ovarian Research. doi:10.1186/s13048-019-0592-3.
2. Noye TM, Lokman NA, Oehler MK, Ricciardelli C. S100A10 and Cancer Hallmarks: Structure, Functions, and its Emerging Role in Ovarian Cancer. Int J Mol Sci. doi:10.3390/ijms19124122.