Nicole M Reusser1, Heather J Dalton2, Sunila Pradeep2, Vianey Gonzalez-Villasana3, Nicholas B Jennings2, Hernan G Vasquez4, Yunfei Wen2, Rajesh Rupaimoole2, Archana S Nagaraja2, Kshipra Gharpure2, Takahito Miyake2, Jie Huang2, Wei Hu2, Gabriel Lopez-Berestein5, Anil K Sood6. 1. Department of Nanomedicine and Bioengineering; The University of Texas Health Science Center at Houston; Houston, TX USA; Department of Gynecologic Oncology and Reproductive Medicine; The University of Texas MD Anderson Cancer Center; Houston, TX USA. 2. Department of Gynecologic Oncology and Reproductive Medicine; The University of Texas MD Anderson Cancer Center; Houston, TX USA. 3. Department of Experimental Therapeutics; The University of Texas MD Anderson Cancer Center; Houston, TX USA. 4. Department of Internal Medicine; The University of Texas Health Science Center at Houston; Houston, TX USA. 5. Department of Nanomedicine and Bioengineering; The University of Texas Health Science Center at Houston; Houston, TX USA; Department of Experimental Therapeutics; The University of Texas MD Anderson Cancer Center; Houston, TX USA; Department of Cancer Biology; The University of Texas MD Anderson Cancer Center; Houston, TX USA; Center for RNA Interference and Non-Coding RNA; The University of Texas MD Anderson Cancer Center; Houston, TX USA. 6. Department of Gynecologic Oncology and Reproductive Medicine; The University of Texas MD Anderson Cancer Center; Houston, TX USA; Department of Cancer Biology; The University of Texas MD Anderson Cancer Center; Houston, TX USA; Center for RNA Interference and Non-Coding RNA; The University of Texas MD Anderson Cancer Center; Houston, TX USA.
Abstract
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.
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.
Authors: Abigail F Welford; Daniela Biziato; Seth B Coffelt; Silvia Nucera; Matthew Fisher; Ferdinando Pucci; Clelia Di Serio; Luigi Naldini; Michele De Palma; Gillian M Tozer; Claire E Lewis Journal: J Clin Invest Date: 2011-04-01 Impact factor: 14.808
Authors: David G DeNardo; Donal J Brennan; Elton Rexhepaj; Brian Ruffell; Stephen L Shiao; Stephen F Madden; William M Gallagher; Nikhil Wadhwani; Scott D Keil; Sharfaa A Junaid; Hope S Rugo; E Shelley Hwang; Karin Jirström; Brian L West; Lisa M Coussens Journal: Cancer Discov Date: 2011-06-01 Impact factor: 39.397
Authors: Ingo J Diel; Ignac Fogelman; Bilal Al-Nawas; Bodo Hoffmeister; Cesar Migliorati; Joseph Gligorov; Kalervo Väänänen; Liisa Pylkkänen; Martin Pecherstorfer; Matti S Aapro Journal: Crit Rev Oncol Hematol Date: 2007-09-12 Impact factor: 6.312
Authors: Molly J Carroll; Kaitlin C Fogg; Harin A Patel; Harris B Krause; Anne-Sophie Mancha; Manish S Patankar; Paul S Weisman; Lisa Barroilhet; Pamela K Kreeger Journal: Cancer Res Date: 2018-05-08 Impact factor: 12.701
Authors: Eli Sihn Samdal Steinskog; Solfrid Johanne Sagstad; Marek Wagner; Tine Veronica Karlsen; Ning Yang; Carl Erik Markhus; Synnøve Yndestad; Helge Wiig; Hans Petter Eikesdal Journal: Oncotarget Date: 2016-07-19