title: Integrin α4 Induces Lymphangiogenesis and Metastasis via Upregulation of VEGF-C in Human Colon Cancer.
abstract: Vascular endothelial growth factor-C (VEGF-C) is a key regulator in lymphangiogenesis, and is overexpressed in various malignancies. Integrin α4β1, a new member of the VEGF-C/VEGF receptor pathway, was found to be overexpressed in melanoma tumors. However, little is known regarding the potential role of integrin α4β1 in lymphangiogenesis and other solid tumors. The aim of this study was to investigate the expression patterns of integrin α4 and VEGF-C in relation to lymphangiogenesis and clinicopathological parameters in human colon cancer. The expression of integrin α4, VEGF-C, and VEGFR-3 was assessed in 71 human colon cancer tissues and 30 paracancerous normal tissues by immunohistochemical staining. Lymphatic microvessel density (LMVD) was measured after D2-40-labeling, and the correlations among different factors were statistically analyzed. The expression of integrin α4, VEGF-C, VEGFR-3, and LMVD was higher in colon cancer tissues compared with the normal paracancerous colon tissues. There was a positive correlation between the expression of integrin α4 and VEGF-C. Integrin α4 and VEGF-C were significantly associated with the clinicopathological parameters (LMVD, Duke's stage, and lymph node metastasis). Kaplan-Meier analyses indicated that patients with high integrin α4 or VEGF-C expression had significantly shorter overall survival and tumor-free survival time. Multivariate analyses suggested that integrin α4 and VEGF-C may serve as independent prognostic factors for human colon cancer. Both integrin α4 and VEGF-C are involved in lymphangiogenesis and lymphatic metastasis. Our results demonstrated that integrin α4 is a novel prognostic indicator for human colon cancer. Anat Rec, 299:741-747, 2016. © 2016 Wiley Periodicals, Inc.
authors.affiliation: Department of Anatomy, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Xiao-Hong
authors.initials: XH
authors.lastname: Lv
authors.affiliation: Department of Anatomy, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Bao-Quan
authors.initials: BQ
authors.lastname: Liu
authors.affiliation: Department of Anatomy, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Xue-Mei
authors.initials: XM
authors.lastname: Li
authors.affiliation: Department of Anatomy, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Xiang-Chen
authors.initials: XC
authors.lastname: Wang
authors.affiliation: Department of Anatomy, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Xin-Lei
authors.initials: XL
authors.lastname: Li
authors.affiliation: Department of Anatomy, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Naila
authors.initials: N
authors.lastname: Ahmed
authors.affiliation: Department of Anatomy, Harbin Medical University, Harbin, People's Republic of China.
authors.forename: Ya-Fang
authors.initials: YF
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000378:metabolism / Q000401:mortality / Q000473:pathology*; D005260:Female; D006801:Humans; D039441:Integrin alpha4 / Q000378:metabolism*; D042583:Lymphangiogenesis / Q000502:physiology*; D008207:Lymphatic Metastasis / Q000473:pathology*; D042601:Lymphatic Vessels / Q000378:metabolism / Q000473:pathology; D008297:Male; D055806:Microvessels / Q000378:metabolism / Q000473:pathology; D008875:Middle Aged; D011379:Prognosis; D015996:Survival Rate; D015854:Up-Regulation; D042582:Vascular Endothelial Growth Factor C / Q000378:metabolism*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism; D055815:Young Adult
chemical_list: D042582:Vascular Endothelial Growth Factor C; D039441:Integrin alpha4; D040321:Vascular Endothelial Growth Factor Receptor-3
keywords: VEGFR-3; colon cancer; integrin α4; lymphatic metastasis; vascular endothelial growth factor-C