title: Effect of vegf gene knockdown on growth of the murine sarcoma cell line MS-K.
abstract: The murine sarcoma cell line MS-K was previously established as a Ki-ras-positive cell line. Inoculation of this cell line under the flank of C3H/HeN mice results in the growth of large tumors with well-developed blood vessels within day 30 of transplantation without any metastasis because MS-K cells produce vascular endothelial growth factor (VEGF). To elucidate the role of VEGF in tumor formation in vivo, stable vegf-knockdown-MS-K clones were obtained using plasmid-based knockdown vectors. Interestingly, tumorigenesis was completely suppressed in a vegf-A-knockdown-MS-K clone [designated MS-K (A-KD)]. Proliferation and colony formation capacity of the MS-K (A-KD) cells in a semi-solid medium under low serum conditions was significantly lower than that of control MS-K (SCR) cells; however, the expression of vegf-receptor 1 (vegf-r-1) was not changed. Addition of the recombinant VEGF-A(165) partially restored the colony formation capacity of MS-K (A-KD) cells and caused the phosphorylation of VEGF-r-1 (Flt-1) in MS-K (Normal) cells. Furthermore, tumorigenicity of the vegf-r-1-knockdown-MS-K clone [designated MS-K (R1-KD)] had obviously delayed or strongly suppressed compared with the MS-K (Normal). These results indicate that Vascular endothelial growth factor-A, produced from MS-K, acts as a growth factor for MS-K cells itself and supports tumor formation in vivo by inducing the blood vessel formation.
authors.affiliation: Department of Cell Science, Faculty of Graduate School of Science and Technology, Niigata University, Nishi-ku, Niigata 950-2181, Japan.
authors.forename: Xiu Y
authors.initials: XY
authors.lastname: Zhong
authors.forename: Asami
authors.initials: A
authors.lastname: Yoshioka
authors.forename: Yuka
authors.initials: Y
authors.lastname: Mashio
authors.forename: Toru
authors.initials: T
authors.lastname: Ikeda
authors.forename: Huijie
authors.initials: H
authors.lastname: Jiang
authors.forename: Maki
authors.initials: M
authors.lastname: Touma
authors.forename: Qiong
authors.initials: Q
authors.lastname: Wu
authors.forename: ChangLiu
authors.initials: C
authors.lastname: Wang
authors.forename: Kenkichi
authors.initials: K
authors.lastname: Sugimoto
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D004195:Disease Models, Animal; D015972:Gene Expression Regulation, Neoplastic / Q000235:genetics; D055785:Gene Knockdown Techniques; D051379:Mice; D008809:Mice, Inbred C3H; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000473:pathology; D012509:Sarcoma / Q000235:genetics* / Q000378:metabolism* / Q000473:pathology; D047368:Tumor Burden / Q000235:genetics; D042461:Vascular Endothelial Growth Factor A / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics; D042442:Vascular Endothelial Growth Factors / Q000235:genetics* / Q000378:metabolism*; D023041:Xenograft Model Antitumor Assays
chemical_list: D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D040281:Vascular Endothelial Growth Factor Receptor-1