TY - JOUR
T1 - Clodronate inhibits tumor angiogenesis in mouse models of ovarian cancer
AU - Reusser, Nicole M.
AU - Dalton, Heather J.
AU - Pradeep, Sunila
AU - Gonzalez-Villasana, Vianey
AU - Jennings, Nicholas B.
AU - Vasquez, Hernan G.
AU - Wen, Yunfei
AU - Rupaimoole, Rajesh
AU - Nagaraja, Archana S.
AU - Gharpure, Kshipra
AU - Miyake, Takahito
AU - Huang, Jie
AU - Hu, Wei
AU - Lopez-Berestein, Gabriel
AU - Sood, Anil K.
PY - 2014/8
Y1 - 2014/8
N2 - 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.
AB - 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.
KW - Anti-angiogenesis
KW - Bisphosphonate
KW - Clodronate
KW - Ovarian cancer
KW - Tumor angiogenesis
KW - Tumor microenvironment
KW - Tumor-associated macrophages
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U2 - 10.4161/cbt.29184
DO - 10.4161/cbt.29184
M3 - Article
C2 - 24841852
AN - SCOPUS:84905487210
SN - 1538-4047
VL - 15
SP - 1061
EP - 1067
JO - Cancer Biology and Therapy
JF - Cancer Biology and Therapy
IS - 8
ER -