Rapid vascular regrowth in tumors after reversal of VEGF inhibition.

Rapid vascular regrowth in tumors after reversal of VEGF inhibition. Research Abstract Details 

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Rapid vascular regrowth in tumors after reversal of VEGF inhibition. Abstract Text:

Inhibitors of VEGF signaling can block angiogenesis and reduce tumor vascularity, but little is known about the reversibility of these changes after treatment ends. In the present study, regrowth of blood vessels in spontaneous RIP-Tag2 tumors and implanted Lewis lung carcinomas in mice was assessed after inhibition of VEGF receptor signaling by AG-013736 or AG-028262 for 7 days. Both agents caused loss of 50%-60% of tumor vasculature. Empty sleeves of basement membrane were left behind. Pericytes also survived but had less alpha-SMA immunoreactivity. One day after drug withdrawal, endothelial sprouts grew into empty sleeves of basement membrane. Vessel patency and connection to the bloodstream followed close behind. By 7 days, tumors were fully revascularized, and the pericyte phenotype returned to baseline. Importantly, the regrown vasculature regressed as much during a second treatment as it did in the first. Inhibition of MMPs or targeting of type IV collagen cryptic sites by antibody HUIV26 did not eliminate the sleeves or slow revascularization. These results suggest that empty sleeves of basement membrane and accompanying pericytes provide a scaffold for rapid revascularization of tumors after removal of anti-VEGF therapy and highlight their importance as potential targets in cancer therapy.

Rapid vascular regrowth in tumors after reversal of VEGF inhibition. Publishing Authors By Initials

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Rapid vascular regrowth in tumors after reversal of VEGF inhibition. Journal Published:

PUBLICATION TYPE: Research Support, Non-U.S. Gov

Journal: The Journal of clinical investigation

VOLUME: 116

Page Numbers: 2610-21

Journal Abbreviation: J. Clin. Invest.

ISSN: 0021-9738

DAY: 3

MONTH: Oct

YEAR: 2006

Rapid vascular regrowth in tumors after reversal of VEGF inhibition. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7802877

Rapid vascular regrowth in tumors after reversal of VEGF inhibition. Keywords Mesh Terms:

KEYWORDS: Vascular Endothelial Growth Factor Recep

MESH TERMS: metabolism

Chemical & Substance for Abstract: Rapid vascular regrowth in tumors after reversal of VEGF inhibition. Information

Substance Name: Matrix Metalloproteinases

Registry Number: EC 3.4.24.-

Grant and Affiliation Information for Rapid vascular regrowth in tumors after reversal of VEGF inhibition.

AFFILIATION: Cardiovascular Research Institute, Comprehensive Cancer Center, and Department of Anatomy, UCSF, San Francisco, California 94143-0452, USA.

Country: United States

AGENCY: United States NCI

GRANT: P50-CA90270

ACRONYM: CA

MEDLINETA: J Clin Invest

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