Department of Physiology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
Department of Pathology, College of Medicine and Health Sciences, Sultan Qaboos University, Muscat, Oman.
PLoS One. 2021 Aug 6;16(8):e0255701. doi: 10.1371/journal.pone.0255701. eCollection 2021.
Ovarian cancer (OC) is characterized by a high morbidity and mortality, highlighting a great need for a better understanding of biological mechanisms that affect OC progression and improving its early detection methods. This study investigates effects of prolactin (PRL) on ovarian cancer cells, analyzes PRL receptors (PRLR) in tissue micro arrays and relates PRLR expression to survival of ovarian cancer. A database, composed of transcript profiles from OC, was searched for PRLR expression and results were put in relation to survival. Expression of PRLR in OC tissue sections and OC cell lines SKOV3, OV2008 and OVSAHO was assessed using immunohistochemistry, western blots and quantitative real-time PCR. The biological function of PRLR was evaluated by proliferation, colony formation and wound healing assays. Levels of PRLR mRNA are related to survival; in epithelial OC a high PRLR mRNA expression is related to a shorter survival. Analysis of a tissue micro array consisting of 84 OC showed that 72% were positive for PRLR immuno-staining. PRLR staining tended to be higher in OC of high grade tumors compared to lower grades. PRLR mRNA and protein can further be detected in OC cell lines. Moreover, in vitro treatment with PRL significantly activated the JAK/STAT pathway. PRLR expression is associated with OC survivals. PRL and its receptor may play an onco-modulatory role and promote tumor aggressiveness in OC. Alternatively, increased PRLR levels may form a base for the development of PRLR antagonist or PRLR antagonist-drug conjugate to increase selective uptake of anti-cancer drugs.
卵巢癌（OC）的发病率和死亡率均较高，这突出表明需要更好地了解影响 OC 进展的生物学机制，并改进其早期检测方法。本研究调查了催乳素（PRL）对卵巢癌细胞的影响，分析了组织微阵列中的 PRL 受体（PRLR），并将 PRLR 表达与卵巢癌的生存相关联。搜索了包含 OC 转录谱的数据库，以寻找 PRLR 表达，并将结果与生存相关联。使用免疫组织化学，Western blot 和定量实时 PCR 评估 OC 组织切片和 OC 细胞系 SKOV3、OV2008 和 OVSAHO 中的 PRLR 表达。通过增殖，集落形成和划痕愈合测定评估 PRLR 的生物学功能。PRLR mRNA 的水平与生存有关；在上皮 OC 中，高 PRLR mRNA 表达与较短的生存时间相关。对包含 84 例 OC 的组织微阵列进行分析表明，72％的 OC 对 PRLR 免疫染色呈阳性。与低等级肿瘤相比，高等级肿瘤的 PRLR 染色倾向更高。还可以在 OC 细胞系中进一步检测到 PRLR mRNA 和蛋白。此外，PRL 体外处理可显著激活 JAK/STAT 途径。PRLR 表达与 OC 存活相关。PRL 及其受体可能在 OC 中发挥致癌调节作用，并促进肿瘤侵袭性。或者，PRLR 水平的增加可能为开发 PRLR 拮抗剂或 PRLR 拮抗剂-药物偶联物奠定基础，以增加抗癌药物的选择性摄取。
