Abstract
BackgroundElevated Plexin-B1 expression has been found in diverse human cancers and in non-neoplastic tissues, and it mediates diverse biological and pathological activities. However, whether or not Plexin-B1 expression is involved in human ovarian tumors remains unclear. In the present study, Plexin-B1 expression was explored in benign and malignant human ovarian tumor tissues. In addition, the impact of Plexin-B1 expression on ovarian cancer cell proliferation, migration and invasion were investigated in vitro.MethodsPlexin-B1 expression was analyzed in normal and benign ovarian tissues and serous ovarian tumors (both borderline and malignant) by immunohistochemical staining, as well as in four human ovarian cancer cell lines (A2780, C13*, SKOV3, and OV2008) by RT-PCR and western blot analyses. Furthermore, endogenous Plexin-B1 expression was suppressed by Plexin-B1 siRNA in SKOV3 cells, which overexpress Plexin-B1. Protein levels of Plexin-B1, AKT and AKTSer473 were examined by western blot analysis. Cell proliferation, migration and invasion were measured with MTT, wound healing and boyden chamber assays, respectively, and the cytoskeleton was monitored via F-actin staining.ResultsExpression levels of Plexin-B1 protein were significantly higher in serous ovarian carcinomas than in normal ovaries or benign ovarian neoplasms, and in the former, Plexin-B1 expression was positively correlated with lymphatic metastasis, and the membrane and cytoplasm of cancer cells stained positively. SKOV3 cells displayed the highest Plexin-B1 expression at both the mRNA and protein levels among the four tested human ovarian cancer cell lines and was selected as a cell model for further in vitro experiments. Plexin-B1 siRNA significantly suppressed phosphorylation of AKT at Ser473 in SKOV3 cells, but it did not alter total AKT expression. In addition, silencing of Plexin-B1 in SKOV3 cells inhibited cell migration and invasion and reorganized the cytoskeleton, whereas cell proliferation was not affected.ConclusionPlexin-B1 expression correlates with malignant phenotypes of serous ovarian tumors, probably via phosphorylation of AKT at Ser473, suggesting that Plexin-B1 might be a useful biomarker and/or a novel therapeutic target.
Highlights
Elevated Plexin-B1 expression has been found in diverse human cancers and in non-neoplastic tissues, and it mediates diverse biological and pathological activities
Expression of Plexin-B1 in human ovarian tissues with different pathological changes To elucidate the expression of Plexin-B1 protein during serous ovarian carcinogenesis and to study the association of Plexin-B1 expression with clinical-pathological parameters, the expression levels of this protein in normal human ovaries, benign ovarian tissue, serous borderline ovarian tumors and malignant ovarian tumors were investigated with immunohistochemistry
In ovarian cystadenocarcinomas, the membrane and cytoplasm of the tumor cells was positive for Plexin-B1 immunostaining (Figure 1D), and a significant difference (P = 0.008) in positive staining was observed between samples with lymph node metastasis (75.00%) and those without lymph node metastasis (44.23%)
Summary
Elevated Plexin-B1 expression has been found in diverse human cancers and in non-neoplastic tissues, and it mediates diverse biological and pathological activities. Whether or not Plexin-B1 expression is involved in human ovarian tumors remains unclear. Plexin-B1 expression was explored in benign and malignant human ovarian tumor tissues. Plexin proteins comprise a large family of trans-membrane receptors for semaphorins, which are secreted, membrane-associated or GPI-anchored proteins originally identified for their role in axon guidance repulsion [1]. Nine plexins are divided into four subfamilies according to their different structures: plexinA1-4, plexinB1-3, plexin-C1 and plexin-D1 [1]. Plexin-A subgroup members bind secreted class III semaphorins by associating with neuropilin-1 and neuropilin-2, and plexin-B members bind their ligands independently [3]. It is known that plexin-B1 binds Sema 4D, plexin-B2 binds Sema 4C and plexin-B3 binds Sema 5A [5]
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