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Oncotarget: Osteoprotegerin rich tumor microenvironment: implications in breast cancer


Here is a link to a video interview with Dr. Neelam Sharma-Walia about this research on the Oncotarget YouTube Channel

Oncotarget published "Osteoprotegerin rich tumor microenvironment: implications in breast cancer" which reported that Osteoprotegerin is a soluble decoy receptor for tumor necrosis factor -related apoptosis inducing ligand.

Besides having anti-osteoclastic activity, OPG is thought to exert a protective anti-apoptotic action in OPG-expressing tumors by overcoming the physiologic mechanism of tumor surveillance exerted by TRAIL.

Along with inhibiting TRAIL induced apoptosis, it can induce proliferation by binding to various cell surface receptors and thus turning on the canonical cell survival and proliferative pathways.

OPG also induces angiogenesis, one of the hallmarks of cancer, thus facilitating tumor growth.

This Oncotarget review is aimed at providing a very informative overview as to how OPG affects cancer progression especially breast cancer.

This Oncotarget review is aimed at providing a very informative overview as to how OPG affects cancer progression especially breast cancer

Dr. Neelam Sharma-Walia from The Chicago Medical School said, "At present, one in eight women in the United States will develop breast cancer"

TME is also rich in various cytokines, chemokines, ECM proteins, growth and angiogenic factors involved in autocrine but also paracrine cell signaling. The field of TME has expanded the understanding of cancer as more than a single factor driven disease.

Rather, cancer biology involves complex reciprocal interaction and co-evolution between cancer cells and host stromal cells, interplay of soluble growth factors and chemokines as the key mediators involved in oncogenic signaling pathways of tumors.

The majority of these are multikinase inhibitors blocking tumor cell growth pathways such as BRAF, Bcr-Abl, c-Kit, vascular endothelial growth factor receptor-1, VEGFR-2, VEGFR-3, PDGFR and colony-stimulating factor-1 receptor.

Proteomic landscape of the breast cancer TME includes diverse factors involved in tumor growth, proliferation, metastasis, vascularity, evading cell death pathways and host immune system.

Figure 3: Pie chart depicting the binding partners of OPG from mass spectrometry analysis. A. pull-down with anti-OPG antibody revealed a myriad of proteins involved in different cellular functions in inflammatory and aggressive breast cancer cells.

Here, the authors focus only on osteoprotegerin as one of the factors present in the TME of inflammatory and invasive breast cancer cell lines, and discuss how it multitasks various functions to drive tumorigenesis.

The Sharma-Walia Research Team concluded in their Oncotarget Review that in a murine model of osteolytic bone metastases of breast cancer, the CRAd armed with shortened OPG -Fc reduced tumor burden in the bone and inhibited osteoclast formation more effectively than an unarmed CRAd suggesting the role of OPG.

Breast cancer development in BRCA1/2 mutation carriers is a consequence of autonomous and nonautonomous cell factors, which serve as excellent targets for cancer prevention.

OPG may become a new biomarker and a target of treatment for patients with colorectal cancer since many studies have revealed the clinicopathologic significance of OPG expression by using clinical tissue samples from patients.

The effects of sustained expression of OPG using a recombinant adeno-associated viral vector in a mouse model of osteolytic breast cancer has clearly indicated the potential of rAAV-OPG therapy for reducing morbidity and mortality in breast cancer patients with osteolytic bone damage.

With all this development in the understanding of OPG, there might be more therapeutic avenues to manipulate OPG to predict and manage aggressive forms of breast cancer.

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DOI - https://doi.org/10.18632/oncotarget.8658

Full text - https://www.oncotarget.com/article/8658/text/

Correspondence to - Neelam Sharma-Walia - neelam.sharma-walia@rosalindfranklin.edu

Keywords - osteoprotegerin, NF-kB, COX-2, PGE2, FASN

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