Abstract
BackgroundSemaphorin 5A has been linked to tumor growth, invasion, and metastasis in pancreatic cancer. However, the role of semaphorin 5A in cervical cancer is not known. Our aim is to investigate the prognostic value of semaphorin 5A and its potential role in lymphangiogenesis and invasion in cervical cancer.MethodsIn this study, pathological features and clinical data of 232 cervical cancer patients were retrospectively reviewed. Semaphorin 5A protein and mRNA expression was detected by immunohistochemistry and quantitative real-time reverse transcription-polymerase chain reaction, respectively. In vitro, we determined the role and mechanistic pathways of semaphorin 5A in tumor progression in cervical carcinoma cell lines.ResultsSemaphorin 5A expression was significantly higher in stage IIb tumors than in stage Ia, Ib, and IIa tumors. High semaphorin 5A expression was significantly associated with pelvic lymph node metastasis, lymphovascular permeation, and poor survival. Semaphorin 5A induced lymphangiogenesis through a plexin-B/Met/vascular endothelial growth factor-C pathway. Semaphorin 5A also increased cervical cancer cell invasion by stimulating the expression and activity of matrix metalloproteinase-2 and matrix metalloproteinase-9 via PI3K/AKT and plexin-B3.ConclusionOur findings indicate that semaphorin 5A may represent a poor prognostic biomarker and anti-metastasis therapeutic target in cervical cancer.
Highlights
Semaphorin 5A has been linked to tumor growth, invasion, and metastasis in pancreatic cancer
Immunostaining demonstrated that SEMA5A was highly expressed in cervical cancer cells from stage IIb tumor tissues, comparable to that seen in nonsmall cell lung carcinoma (NSCLC), which was used as the positive control (Additional file 1: Figure S1B), but was expressed only at very low levels in stage Ia, Ib, and IIa tumor tissues (Fig. 1)
The reverse transcription-polymerase chain reaction (RT-PCR) analysis shows that the data of SEMA5A mRNA is increased in stage IIb tumors and supports SEMA5A protein expression demonstrated by IHC analysis
Summary
Semaphorin 5A has been linked to tumor growth, invasion, and metastasis in pancreatic cancer. The role of semaphorin 5A in cervical cancer is not known. Our aim is to investigate the prognostic value of semaphorin 5A and its potential role in lymphangiogenesis and invasion in cervical cancer. Lymph node metastasis (LNM) is an important factor for tumor recurrence and disease progression. The prognosis for patients with lymph node metastases is inversely correlated to the number of nodes involved. Bilateral lymph node involvement confers a much poorer prognosis than unilateral involvement. Semaphorins, a large family of secreted glycosylphosphatidylinositol-linked transmembrane proteins, is first identified for their central role in axonal guidance and nervous system development [4, 5]. Recent studies have suggested that the semaphorin family is widely distributed in many tissues and organs apart from the nervous system and is involved in cell migration, blood
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