Heterogeneity among RIP-Tag2 insulinomas allows vascular endothelial growth factor-A independent tumor expansion as revealed by studies in Shb mutant mice: implications for tumor angiogenesis.

Molecular Oncology
Björn AkerblomMichael Welsh

Abstract

The Shb adapter protein is a signaling intermediate that operates downstream of vascular endothelial growth factor receptor-2 (VEGFR-2) in endothelial cells. The Shb knockout mouse displays a dysfunctional microvasculature and impaired growth of subcutaneously implanted tumor cells. We decided to investigate tumor growth and angiogenesis in the absence of Shb in an inheritable tumor model, the RIP-Tag2 mouse, which produces insulinomas in a manner highly dependent on de novo angiogenesis. We observed a reduced tumor incidence and burden in both RIP-Tag2 Shb-/- and RIP-Tag2 Shb+/- mice. This correlated with a reduced microvascular density, measured as a percentage of insulinoma area positive for CD31 staining, and altered vascular morphology. However, treatment with a VEGF-A blocking antibody was without effect on the Shb mutant tumor volume whereas it significantly inhibited tumor volume in the wild-type mice, suggesting that in mice with reduced Shb expression tumor angiogenesis was primarily sustained by VEGF-A independent pathway(s). This notion was further substantiated by gene expression analysis of angiogenic markers showing reduced VEGF-A expression in Shb-deficient tumors. Considerable heterogeneity with respect to the ...Continue Reading

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Jan 13, 2011·BMC Immunology·Karin GustafssonMichael Welsh

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Citations

Oct 23, 2015·Journal of Molecular Endocrinology·Michael WelshBjörn Åkerblom
Aug 12, 2015·Molecular and Cellular Endocrinology·Run Yu
Dec 12, 2012·Journal of Internal Medicine·L Claesson-Welsh, M Welsh
Mar 26, 2013·Molecular Oncology·Lauri EklundKari Alitalo
Oct 7, 2017·Tumour Biology : the Journal of the International Society for Oncodevelopmental Biology and Medicine·Maria JamalpourMichael Welsh
May 23, 2020·International Journal of Cancer. Journal International Du Cancer·Qi HeMichael Welsh

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