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

研究成果: ジャーナルへの寄稿学術誌査読

32 被引用数 (Scopus)

抄録

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.

本文言語英語
ページ(範囲)886-896
ページ数11
ジャーナルNeoplasia
10
8
DOI
出版ステータス出版済み - 8月 2008
外部発表はい

!!!All Science Journal Classification (ASJC) codes

  • 癌研究

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