Inhibition of vessel permeability by TNP-470 and its polymer conjugate, caplostatin

Ronit Satchi-Fainaro, Roni Mamluk, Ling Wang, Sarah M. Short, Janice A. Nagy, Dian Feng, Ann M. Dvorak, Harold F. Dvorak, Mark Puder, Debabrata Mukhopadhyay, Judah Folkman

Research output: Contribution to journalArticlepeer-review

147 Scopus citations


Angiogenesis inhibitors, such as TNP-470 and the nontoxic HPMA copolymer-TNP-470 (caplostatin), are emerging as a class of anticancer drugs. We report that TNP-470 and caplostatin inhibit vascular hyperpermeability of tumor blood vessels as well as that induced in mouse skin by different mediators. Treatment with TNP-470 or angiostatin for 3 days was sufficient to reduce permeability of tumor blood vessels, delayed-type hypersensitivity, and pulmonary edema induced by IL-2. TNP-470 also inhibited VPF/VEGF-induced phosphorylation of VEGFR-2, calcium influx, and RhoA activation in endothelial cells. These results identify an activity of TNP-470, that of inhibiting vessel hyperpermeability. This activity likely contributes to TNP-470's antiangiogenic effect and suggests that caplostatin can be used in the treatment of cancer and inflammation.

Original languageEnglish (US)
Pages (from-to)251-261
Number of pages11
JournalCancer cell
Issue number3
StatePublished - Mar 2005

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research


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