title: Recombinant canstatin inhibits VEGF-A-induced lymphangiogenesis and metastasis in an oral squamous cell carcinoma SCC-VII animal model.
abstract: We describe the inhibitory effects of recombinant canstatin on tumor growth and lymphangiogenesis induced by an oral squamous cell carcinoma (SCC) using an orthotropic oral SCC animal model. Recombinant canstatin treatment decreased final tumor volumes and weights, as well as densities of blood and lymphatic vessels. Lung metastasis of oral SCC was significantly reduced in recombinant canstatin-treated animals. Recombinant canstatin reduced vascular endothelial growth factor (VEGF)-A expression in SCC-VII cells treated with the hypoxia mimetic agent, CoCl2. VEGF-A induced in vivo lymphatic vessel formation in a Matrigel plug, but this was remarkably reduced in a recombinant canstatin-treated Matrigel. Recombinant canstatin suppressed the expression of vascular endothelial growth factor receptors (VEGFR)-1 and -2 stimulated by VEGF-A. Based on immunohistochemical analysis, recombinant canstatin significantly reduced the expression of VEGF-A, VEGFR-1, and -2 in SCC-VII-induced tumors. Recombinant canstatin did not affect the expression of VEGF-C or VEGFR-3. In addition, recombinant canstatin suppressed the VEGF-A-induced phosphorylation of VEGFR-1 and -2. Our results indicate that recombinant canstatin exhibits antitumoral and antilymphangiogenic activities against oral SCC cells. Antilymphangiogenic signaling by recombinant canstatin is probably mediated by the suppression of the integrin αvβ3/VEGFR-1 and/or -2 signaling induced by VEGF-A. Our results also suggest that recombinant canstatin has a high potential to inhibit oral SCC-induced tumors and lymphatic metastasis.
authors.affiliation: Department of Genetic Engineering and Graduate School of Biotechnology, Kyung Hee University, Yongin, 17104, Korea.
authors.forename: Jeon
authors.initials: J
authors.lastname: Hwang-Bo
authors.affiliation: Department of Genetic Engineering and Graduate School of Biotechnology, Kyung Hee University, Yongin, 17104, Korea.
authors.forename: Jong-Hwa
authors.initials: JH
authors.lastname: Park
authors.affiliation: Department of Genetic Engineering and Graduate School of Biotechnology, Kyung Hee University, Yongin, 17104, Korea.
authors.forename: Mun Gyeong
authors.initials: MG
authors.lastname: Bae
authors.affiliation: Department of Genetic Engineering and Graduate School of Biotechnology, Kyung Hee University, Yongin, 17104, Korea. ischung@khu.ac.kr.
authors.forename: In Sik
authors.initials: IS
authors.lastname: Chung
mesh_terms: D000818:Animals; D002294:Carcinoma, Squamous Cell / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D045744:Cell Line, Tumor; D024141:Collagen Type IV / Q000008:administration & dosage* / Q000494:pharmacology; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D006801:Humans; D008175:Lung Neoplasms / Q000188:drug therapy* / Q000378:metabolism; D042583:Lymphangiogenesis / Q000187:drug effects*; D051379:Mice; D009062:Mouth Neoplasms / Q000188:drug therapy* / Q000378:metabolism / Q000473:pathology; D011994:Recombinant Proteins / Q000008:administration & dosage / Q000494:pharmacology; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism*; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism; D023041:Xenograft Model Antitumor Assays
chemical_list: D024141:Collagen Type IV; D011994:Recombinant Proteins; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse; C000592875:Kdr protein, mouse; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2
keywords: Canstatin; SCC-VII; VEGF-A; lymphangiogenesis; oral squamous cell carcinoma