Clodronate inhibits tumor angiogenesis in mouse models of ovarian cancer. Cancer Biol Ther 2014 Aug;15(8):1061-7
Date
05/21/2014Pubmed ID
24841852Pubmed Central ID
PMC4119073DOI
10.4161/cbt.29184Scopus ID
2-s2.0-84905487210 (requires institutional sign-in at Scopus site) 34 CitationsAbstract
PURPOSE: Bisphosphonates have been shown to inhibit and deplete macrophages. The effects of bisphosphonates on other cell types in the tumor microenvironment have been insufficiently studied. Here, we sought to determine the effects of bisphosphonates on ovarian cancer angiogenesis and growth via their effect on the microenvironment, including macrophage, endothelial and tumor cell populations.
EXPERIMENTAL DESIGN: Using in vitro and in vivo models, we examined the effects of clodronate on angiogenesis and macrophage density, and the overall effect of clodronate on tumor size and metastasis.
RESULTS: Clodronate inhibited the secretion of pro-angiogenic cytokines by endothelial cells and macrophages, and decreased endothelial migration and capillary tube formation. In treated mice, clodronate significantly decreased tumor size, number of tumor nodules, number of tumor-associated macrophages and tumor capillary density.
CONCLUSIONS: Clodronate is a potent inhibitor of tumor angiogenesis. These results highlight clodronate as a potential therapeutic for cancer.
Author List
Reusser NM, Dalton HJ, Pradeep S, Gonzalez-Villasana V, Jennings NB, Vasquez HG, Wen Y, Rupaimoole R, Nagaraja AS, Gharpure K, Miyake T, Huang J, Hu W, Lopez-Berestein G, Sood AKAuthor
Sunila Pradeep PhD Associate Professor in the Obstetrics and Gynecology department at Medical College of WisconsinMESH terms used to index this publication - Major topics in bold
Angiogenesis InhibitorsAnimals
Bone Density Conservation Agents
Cell Line, Tumor
Cell Movement
Clodronic Acid
Cytokines
Endothelial Cells
Female
Humans
Macrophages
Mice, Inbred C57BL
Ovarian Neoplasms
