1. Gallium, a promising candidate to disrupt the vicious cycle driving osteolytic metastases.
- Author
-
Strazic-Geljic I, Guberovic I, Didak B, Schmid-Antomarchi H, Schmid-Alliana A, Boukhechba F, Bouler JM, Scimeca JC, and Verron E
- Subjects
- Adenocarcinoma metabolism, Adenocarcinoma pathology, Adenocarcinoma secondary, Animals, Bone Neoplasms metabolism, Bone Neoplasms pathology, Bone Neoplasms secondary, Breast Neoplasms drug therapy, Breast Neoplasms metabolism, Breast Neoplasms pathology, Cell Communication drug effects, Cell Line, Tumor, Cell Proliferation drug effects, Cell Survival drug effects, Clone Cells, Culture Media, Conditioned metabolism, Female, Gene Expression Regulation, Neoplastic drug effects, Humans, Mice, Osteoclasts metabolism, Osteoclasts pathology, Osteogenesis drug effects, RAW 264.7 Cells, Transforming Growth Factor beta1 antagonists & inhibitors, Transforming Growth Factor beta1 metabolism, Adenocarcinoma therapy, Anticarcinogenic Agents pharmacology, Bone Density Conservation Agents pharmacology, Bone Neoplasms prevention & control, Gallium pharmacology, Osteoclasts drug effects, Osteolysis prevention & control
- Abstract
Bone metastases of breast cancer typically lead to a severe osteolysis due to an excessive osteoclastic activity. On the other hand, the semi-metallic element gallium (Ga) displays an inhibitory action on osteoclasts, and therefore on bone resorption, as well as antitumour properties. Thus, we explored in vitro Ga effects on osteoclastogenesis in an aggressive bone metastatic environment based on the culture of pre-osteoclast RAW 264.7 cells with conditioned medium from metastatic breast tumour cells, i.e. the breast tumour cell line model MDA-MB-231 and its bone-seeking clone MDA-231BO. We first observed that Ga dose-dependently inhibited the tumour cells-induced osteoclastic differentiation of RAW 264.7 cells. To mimic a more aggressive environment where pro-tumourigenic factors are released from bone matrix due to osteoclastic resorption, metastatic breast tumour cells were stimulated with TGF-β, a mayor cytokine in bone metastasis vicious cycle. In these conditions, we observed that Ga still inhibited cancer cells-driven osteoclastogenesis. Lastly, we evidenced that Ga affected directly and strongly the proliferation/viability of both cancer cell lines, as well as the expression of major osteolytic factors in MDA-231BO cells. With the exception of two small scale clinical studies from 1980s, this is the first time that antitumour properties of Ga have been specifically studied in the context of bone metastases. Our data strongly suggest that, through its action against the vicious cycle involving bone cells and tumour cells, Ga represents a relevant and promising candidate for the local treatment of bone metastases in patients with breast cancer., (Copyright © 2016 Elsevier Inc. All rights reserved.)
- Published
- 2016
- Full Text
- View/download PDF