Abstract
BackgroundThe interaction of vascular endothelial growth factor-C (VEGF-C)/VEGF-D/VEGF receptor-3 is considered to be a major driver of lymphangiogenesis, however the mechanism of this process remains unclear. We aimed to investigate the possible lymphangiogenic significance of synaptonemal complex protein 3 (SCP3) in non-small cell lung cancer (NSCLC).MethodsThe expression of SCP3, VEGF-C, and VEGF-D were measured and examined a correlation between SCP3 and VEGF-C or VEGF-D in various human lung cancer cell lines. Subsequently, we assessed SCP3, VEGF-A, VEGF-B, VEGF-C, and VEGF-D expression in archival tumor tissues from 89 NSCLC patients with lymph node (LN) metastasis by combined immunohistochemistry with quantitative digital image analysis.ResultsPositive correlations between SCP3 and VEGF-C expression (R2 = 0.743) and VEGF-D expression (R2 = 0.932) were detected in various human lung cancer cell lines. The high expression of SCP3, VEGF-A, VEGF-B, VEGF-C, and VEGF-D were detected in 24 (27.0%), 22 (24.7%), 27 (30.3%), 27 (30.3%), and 24 cases (27.0%), respectively. Notably, SCP3 positively correlated with VEGF-C and VEGF-D expression (for both, P < 0.001) and negatively correlated with VEGF-A and VEGF-B expression (P = 0.029 and P = 0.026, respectively). In multivariate analysis of patients with LN metastasis, SCP3 expression predicted worse overall survival (hazard ratio = 1.86, P = 0.008).ConclusionsSCP3 is associated with lymphangiogenesis and provides insight into the SCP3-VEGF-C/VEGF-D axis based cancer therapy strategy.
Highlights
The interaction of vascular endothelial growth factor-C (VEGF-C)/VEGF-D/VEGF receptor-3 is consid‐ ered to be a major driver of lymphangiogenesis, the mechanism of this process remains unclear
Relationship between synaptonemal complex protein 3 (SCP3) and VEGF‐C or VEGF‐D expression in human lung cancer cells Given that SCP3 had been implicated in cervical cancer and metastasis to lymph nodes, we decided to examine its role in lung cancer
We further examined whether the relationship between SCP3 and VEGF-C or SCP3 and VEGF-D was conserved in human lung cancer cells
Summary
The interaction of vascular endothelial growth factor-C (VEGF-C)/VEGF-D/VEGF receptor-3 is consid‐ ered to be a major driver of lymphangiogenesis, the mechanism of this process remains unclear. We aimed to investigate the possible lymphangiogenic significance of synaptonemal complex protein 3 (SCP3) in non-small cell lung cancer (NSCLC). Angiogenesis and lymphangiogenesis play key roles in tumor growth and metastasis in non-small cell lung cancer (NSCLC). The significance of angiogenesis for tumor growth and metastasis has been well understood, the molecular mechanisms of lymphangiogenesis and lymphatic metastasis in tumor metastasis remain unclear [5]. The members of the vascular endothelial growth factor (VEGF) family are considered to be major mediators of both tumor angiogenesis and lymphangiogenesis [6]. Among the VEGF family members, VEGF-C and VEGFD are known as key molecules that mediate the formation of tumor lymphatics as well as metastatic spread of tumor cells to lymph nodes via vascular endothelial growth factor-3 (VEGFR-3) [4, 5, 7]. The prognostic significance of potential lymphangiogenic markers remains controversial [9]
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