纤维连接蛋白受体ITGA5在喉鳞状细胞癌(LSCC)样品中高表达,与不良生存率有关。然而,潜在机制尚不清楚.为了阐明ITGA5在LSCC进展中的调节作用,我们研究了ITGA5表达对淋巴管生成的影响,迁移,和侵袭的LSCC细胞在体外和体内使用免疫组织化学,siRNA转染,qRT-PCR,西方印迹,酶联免疫吸附测定,流式细胞术,Transwell共同文化,管形成,细胞迁移,和入侵检测,和皮下移植瘤模型.ITGA5在LSCC组织中的表达较高,并与淋巴结转移和T分期有关。此外,ITGA5表达与VEGF-C表达呈显著正相关,ITGA5高表达患者的淋巴管密度明显高于ITGA5低表达患者。此外,体外研究发现,下调ITGA5的表达不仅抑制VEGF-C的表达和分泌,同时也抑制了人淋巴管内皮细胞(HLECs)的成管能力和LSCC细胞的迁移和侵袭能力,而外源性VEGF-C的补充逆转了这些现象。此外,肿瘤异种移植实验表明si-ITGA5在体内抑制了TU212衍生肿瘤的生长和转移。我们的发现表明,ITGA5通过增强VEGF-C的表达和分泌来诱导淋巴管生成和LSCC细胞的迁移和侵袭。
ITGA5, a fibronectin receptor was highly expressed in laryngeal squamous cell carcinoma (LSCC) samples and was related to poor survival. However, the potential mechanism remains unclear. To elucidate the regulatory role of
ITGA5 in LSCC progression, we investigated the effect of
ITGA5 expression on lymphangiogenesis, migration, and invasion of LSCC cells in vitro and in vivo using immunohistochemistry, siRNA transfection, qRT-PCR, western blotting, enzyme-linked immunosorbent assay, flow cytometry, transwell co-culture, tube formation, cell migration, and invasion assays, and a subcutaneous graft tumor model. The expression of
ITGA5 was higher in the LSCC tissues and linked to lymph node metastasis and T staging. Moreover, ITGA5 expression was significantly positively correlated with VEGF-C expression, and the lymphatic vessel density of patients with high
ITGA5 expression was noticeably higher than that of patients with low
ITGA5 expression. Additionally, it was found in vitro that downregulation of ITGA5 expression not only inhibited the expression and secretion of VEGF-C, but also suppressed the tube-forming ability of human lymphatic endothelial cells (HLECs) and the migration and invasion ability of LSCC cells, while exogenous VEGF-C supplementation reversed these phenomena. Furthermore, a tumor xenograft assay showed that si-ITGA5 restrained the growth and metastasis of TU212-derived tumors in vivo. Our findings suggested that ITGA5 induces lymphangiogenesis and LSCC cell migration and invasion by enhancing VEGF-C expression and secretion.