Inhibition of tumor cell invasion and angiogenesis by motuporamines

Citation
Cd. Roskelley et al., Inhibition of tumor cell invasion and angiogenesis by motuporamines, CANCER RES, 61(18), 2001, pp. 6788-6794
Citations number
26
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Oncology,"Onconogenesis & Cancer Research
Journal title
CANCER RESEARCH
ISSN journal
0008-5472 → ACNP
Volume
61
Issue
18
Year of publication
2001
Pages
6788 - 6794
Database
ISI
SICI code
0008-5472(20010915)61:18<6788:IOTCIA>2.0.ZU;2-F
Abstract
Tissue invasion is an important determinant of angiogenesis and metastasis and constitutes an attractive target for cancer therapy. We have developed an assay to identify agents that inhibit invasion by mechanisms other than inhibition of cell attachment or cytotoxicity. A screen of marine sponge ex tracts identified motuporamines as micromolar inhibitors of invasion of bas ement membrane gels by MDA-231 breast carcinoma, PC-3 prostate carcinoma, a nd U-87 and U-251 glioma cells. Motuporamine C inhibits cell migration in m onolayer cultures and impairs actin-mediated membrane ruffling at the leadi ng edge of lamellae. Motuporamine C also reduces beta1-integrin activation, raising the possibility that it interferes with "inside-out" signaling to integrins. In addition, motuporamine C inhibits angiogenesis in an in vitro sprouting assay with human endothelial cells and an in vivo chick chorioal lantoic membrane assay. The motuporamines show little or no toxicity or inh ibition of cell proliferation, and they are structurally simple and easy to synthesize, making them attractive drug candidates.