PMID- 37338646 OWN - NLM STAT- Publisher LR - 20231021 IS - 1615-6102 (Electronic) IS - 0033-183X (Linking) VI - 260 IP - 6 DP - 2023 Nov TI - Downregulation of ITGA5 inhibits lymphangiogenesis and cell migration and invasion in male laryngeal squamous cell carcinoma. PG - 1569-1580 LID - 10.1007/s00709-023-01873-3 [doi] AB - 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. CI - (c) 2023. The Author(s), under exclusive licence to Springer-Verlag GmbH Austria, part of Springer Nature. FAU - Wang, Xiaoting AU - Wang X AD - Central Laboratory, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, 350001, Fujian, China. FAU - Huang, Jun AU - Huang J AD - Central Laboratory, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, 350001, Fujian, China. AD - Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, China. FAU - You, Ruolan AU - You R AD - Central Laboratory, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, 350001, Fujian, China. FAU - Hou, Diyu AU - Hou D AD - Central Laboratory, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, 350001, Fujian, China. FAU - Liu, Jingru AU - Liu J AD - Central Laboratory, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, 350001, Fujian, China. FAU - Wu, Long AU - Wu L AD - Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, China. FAU - Yao, Meihong AU - Yao M AD - Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, China. FAU - Yang, Fuwen AU - Yang F AD - Department of Otorhinolaryngology, Head and Neck Surgery, The 900th Hospital of the People's Liberation Army Joint Service Support Force, 156 North Xi-er Huan Road, Fuzhou, 350025, Fujian, China. puwenyang@163.com. FAU - Huang, Huifang AU - Huang H AUID- ORCID: 0000-0002-8548-028X AD - Central Laboratory, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, 350001, Fujian, China. huanghuif@fjmu.edu.cn. LA - eng PT - Journal Article DEP - 20230620 PL - Austria TA - Protoplasma JT - Protoplasma JID - 9806853 SB - IM OTO - NOTNLM OT - ITGA5 OT - Laryngeal squamous cell carcinoma OT - Lymphangiogenesis OT - Metastasis OT - VEGF-C EDAT- 2023/06/20 13:10 MHDA- 2023/06/20 13:10 CRDT- 2023/06/20 11:09 PHST- 2023/02/28 00:00 [received] PHST- 2023/06/09 00:00 [accepted] PHST- 2023/06/20 13:10 [pubmed] PHST- 2023/06/20 13:10 [medline] PHST- 2023/06/20 11:09 [entrez] AID - 10.1007/s00709-023-01873-3 [pii] AID - 10.1007/s00709-023-01873-3 [doi] PST - ppublish SO - Protoplasma. 2023 Nov;260(6):1569-1580. doi: 10.1007/s00709-023-01873-3. Epub 2023 Jun 20.