Inhibition of vessel permeability by TNP-470 and its polymer conjugate, caplostatin. Cancer Cell 2005 Mar;7(3):251-61
Date
03/16/2005Pubmed ID
15766663DOI
10.1016/j.ccr.2005.02.007Scopus ID
2-s2.0-20244381828 (requires institutional sign-in at Scopus site) 169 CitationsAbstract
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.
Author List
Satchi-Fainaro R, Mamluk R, Wang L, Short SM, Nagy JA, Feng D, Dvorak AM, Dvorak HF, Puder M, Mukhopadhyay D, Folkman JMESH terms used to index this publication - Major topics in bold
Angiogenesis InhibitorsAngiostatins
Animals
Calcium
Capillaries
Capillary Permeability
Cell Movement
Cyclohexanes
Endothelial Cells
Female
Hypersensitivity, Delayed
Interleukin-2
Male
Mice
Mice, Inbred C57BL
Mice, SCID
Mitogen-Activated Protein Kinases
Neoplasms
Pulmonary Edema
Sesquiterpenes
Skin
Vascular Endothelial Growth Factor A
Vascular Endothelial Growth Factor Receptor-2
rhoA GTP-Binding Protein
