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 journalArticle

146 Scopus citations

Abstract

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
Volume7
Issue number3
DOIs
StatePublished - Mar 2005

ASJC Scopus subject areas

  • Oncology
  • Cell Biology
  • Cancer Research

Fingerprint Dive into the research topics of 'Inhibition of vessel permeability by TNP-470 and its polymer conjugate, caplostatin'. Together they form a unique fingerprint.

  • Cite this

    Satchi-Fainaro, R., Mamluk, R., Wang, L., Short, S. M., Nagy, J. A., Feng, D., Dvorak, A. M., Dvorak, H. F., Puder, M., Mukhopadhyay, D., & Folkman, J. (2005). Inhibition of vessel permeability by TNP-470 and its polymer conjugate, caplostatin. Cancer cell, 7(3), 251-261. https://doi.org/10.1016/j.ccr.2005.02.007