Thrombospondin 1 and vasoactive agents indirectly alter tumor blood flow

Jeff S. Isenberg, Fuminori Hyodo, Lisa A. Ridnour, Caitlin S. Shannon, David A. Wink, Murali C. Krishna, David D. Roberts

Research output: Contribution to journalArticle

26 Citations (Scopus)

Abstract

Nitric oxide (NO) plays important physiological roles in the vasculature to regulate angiogenesis, blood flow, and hemostasis. In solid tumors, NO is generally acknowledged to mediate angiogenic responses to several growth factors. This contrasts with conflicting evidence that NO can acutely increase tumor perfusion through local vasodilation or diminish perfusion by preferential relaxation of peripheral vascular beds outside the tumor. Because thrombospondin 1 (TSP1) is an important physiological antagonist of NO in vascular cells, we examined whether, in addition to inhibiting tumor angiogenesis, TSP1 can acutely regulate tumor blood flow. We assessed this activity of TSP1 in the context of perfusion responses to NO as a vasodilator and epinephrine as a vasoconstrictor. Nitric oxide treatment of wild type and TSP1 null mice decreased perfusion of a syngeneic melanoma, whereas epinephrine transiently increased tumor perfusion. Acute vasoactive responses were also independent of the level of tumor-expressed TSP1 in a melanoma xenograft, but recovery of basal perfusion was modulated by TSP1 expression. In contrast, overexpression of truncated TSP1 lacking part of its CD47 binding domain lacked this modulating activity. These data indicate that TSP1 primarily regulates long-term vascular responses in tumors, in part, because the tumor vasculature has a limited capacity to acutely respond to vasoactive agents.

Original languageEnglish
Pages (from-to)886-896
Number of pages11
JournalNeoplasia
Volume10
Issue number8
DOIs
Publication statusPublished - Aug 2008

All Science Journal Classification (ASJC) codes

  • Cancer Research

Fingerprint Dive into the research topics of 'Thrombospondin 1 and vasoactive agents indirectly alter tumor blood flow'. Together they form a unique fingerprint.

  • Cite this

    Isenberg, J. S., Hyodo, F., Ridnour, L. A., Shannon, C. S., Wink, D. A., Krishna, M. C., & Roberts, D. D. (2008). Thrombospondin 1 and vasoactive agents indirectly alter tumor blood flow. Neoplasia, 10(8), 886-896. https://doi.org/10.1593/neo.08264