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Downregulation of ITGA5 inhibits lymphangiogenesis and cell migration and invasion in male laryngeal squamous cell carcinoma

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Abstract

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.

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Acknowledgements

We would like to thank Editage (www.editage.com) for English language editing.

Funding

This work was supported by the National Natural Science Foundation of China (grant number: 81902125); Fujian Provincial Natural Fund (grant number: 2019J01460); Joint Funds for the Innovation of Science and Technology, Fujian Province (grant number: 2018Y9020); and Government-funded Project of the Construction of High-level Laboratory (grant number: Min201704).

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Author notes

  1. Xiaoting Wang and Jun Huang contributed equally to this work.

Authors and Affiliations

  1. Central Laboratory, Fujian Medical University Union Hospital, 29 Xinquan Road, Fuzhou, 350001, Fujian, China

    Xiaoting Wang, Jun Huang, Ruolan You, Diyu Hou, Jingru Liu & Huifang Huang

  2. Department of Clinical Laboratory, Fujian Medical University Union Hospital, Fuzhou, China

    Jun Huang

  3. Department of Pathology, Fujian Medical University Union Hospital, Fuzhou, China

    Long Wu & Meihong Yao

  4. 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

    Fuwen Yang

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  1. Xiaoting Wang
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Correspondence to Fuwen Yang or Huifang Huang.

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Ethics approval

This study was approved by the Ethics Committee of the Fujian Medical University Union Hospital (approval number: 2020KY056). All animal experimental procedures were approved by the Animal Care and Use Committee of the 900th Hospital of the People’s Liberation Army Joint Service Support Force (2020-044) and conducted in accordance with the U.K. Animals (Scientific Procedures) Act.

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Wang, X., Huang, J., You, R. et al. Downregulation of ITGA5 inhibits lymphangiogenesis and cell migration and invasion in male laryngeal squamous cell carcinoma. Protoplasma 260, 1569–1580 (2023). https://doi.org/10.1007/s00709-023-01873-3

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