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Clodronate inhibits tumor angiogenesis in mouse models of ovarian cancer
Nicole M Reusser1, Heather J Dalton2, Sunila Pradeep2
1Department 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.
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.
Insights
Clodronate, a bisphosphonate, effectively inhibits ovarian cancer angiogenesis and growth by targeting macrophages and endothelial cells. This study highlights its potential as a novel cancer therapeutic.
Area of Science:
- Oncology
- Immunology
- Cell Biology
Background:
- Bisphosphonates are known to affect macrophages.
- Limited research exists on bisphosphonate effects on the broader tumor microenvironment.
- Ovarian cancer progression involves angiogenesis and immune cell interactions.
Purpose of the Study:
- To investigate bisphosphonate effects on ovarian cancer angiogenesis.
- To determine bisphosphonate impact on tumor microenvironment cell populations (macrophages, endothelial cells, tumor cells).
- To evaluate bisphosphonates' influence on ovarian cancer growth and metastasis.
Main Methods:
- In vitro and in vivo experimental models were utilized.
- Clodronate's effects on angiogenesis and macrophage density were examined.
- Tumor size and metastasis were assessed in treated animal models.
Main Results:
- Clodronate suppressed pro-angiogenic cytokine secretion from endothelial cells and macrophages.
- Endothelial cell migration and capillary tube formation were reduced by clodronate.
- In vivo, clodronate significantly decreased tumor size, nodule number, macrophage density, and tumor vascularity.
Conclusions:
- Clodronate demonstrates potent inhibition of tumor angiogenesis.
- The findings suggest clodronate as a promising therapeutic agent for cancer treatment.
- Bisphosphonates can modulate the tumor microenvironment to impede cancer progression.