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Osteopontin induces angiogenesis of murine neuroblastoma cells in mice
Author(s) -
Takahashi Fumiyuki,
Akutagawa Shigeru,
Fukumoto Hisao,
Tsukiyama Shoji,
Ohe Yuichiro,
Takahashi Kazuhisa,
Fukuchi Yoshinosuke,
Saijo Nagahiro,
Nishio Kazuto
Publication year - 2002
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.10261
Subject(s) - angiogenesis , osteopontin , transfection , umbilical vein , neovascularization , biology , neuroblastoma , cancer research , human umbilical vein endothelial cell , endothelial stem cell , vascular endothelial growth factor , microbiology and biotechnology , immunology , cell culture , in vitro , vegf receptors , biochemistry , genetics
Angiogenesis is an essential process for tumor growth and is regulated by tumor‐derived angiogenic cytokines. Osteopontin (OPN) is one of the cytokines produced by various tumor cells and is suggested to be involved in angiogenesis by upregulating endothelial cell migration in cooperation with vascular endothelial cell growth factor (VEGF). To provide evidence of OPN involvement in a causal role in tumor angiogenesis, we generated a stable transfectant from murine neuroblastoma C1300 cells to constitutively secrete high levels of murine OPN. The OPN mRNA expression and protein secretion were confirmed by RT‐PCR and ELISA, respectively. The biological activity of secreted OPN was determined with migration assay by using human umbilical vein endothelial cells (HUVEC). Transfection with OPN gene did not increase VEGF production and did not affect gene expression of other angiogenic factors confirmed by complementary DNA macroarray system. To demonstrate the effect of OPN on tumor‐induced angiogenesis in vivo , millipore chambers containing OPN‐transfected or control cells were implanted to the dorsal air sac of mice. The OPN‐transfected cells significantly induced neovascularization in comparison to the control cells in mice. Conclusively, these results provide direct evidence of OPN involvement in the role of tumor angiogenesis. © 2002 Wiley‐Liss, Inc.