Suppression of NADPH Oxidase Activity May Slow the Expansion of Osteolytic Bone Metastases
AbstractLysophosphatidic acid (LPA), generated in the microenvironment of cancer cells, can drive the proliferation, invasion, and migration of cancer cells by activating G protein-coupled LPA receptors. Moreover, in cancer cells that have metastasized to bone, LPA signaling can promote osteolysis by inducing cancer cell production of cytokines, such as IL-6 and IL-8, which can stimulate osteoblasts to secrete RANKL, a key promoter of osteoclastogenesis. Indeed, in cancers prone to metastasize to bone, LPA appears to be a major driver of the expansion of osteolytic bone metastases. Activation of NADPH oxidase has been shown to play a mediating role in the signaling pathways by which LPA, as well as RANKL, promote osteolysis. In addition, there is reason to suspect that Nox4 activation is a mediator of the feed-forward mechanism whereby release of TGF-beta from bone matrix by osteolysis promotes expression of PTHrP in cancer cells, and thereby induces further osteolysis. Hence, measures which can down-regulate NADPH oxidase activity may have potential for slowing the expansion of osteolytic bone metastases in cancer patients. Phycocyanin and high-dose statins may have utility in this regard, and could be contemplated as complements to bisphosphonates or denosumab for the prevention and control of osteolytic lesions. Ingestion of omega-3-rich flaxseed or fish oil may also have potential for controlling osteolysis in cancer patients. View Full-Text
Share & Cite This Article
McCarty, M.F.; DiNicolantonio, J. Suppression of NADPH Oxidase Activity May Slow the Expansion of Osteolytic Bone Metastases. Healthcare 2016, 4, 60.
McCarty MF, DiNicolantonio J. Suppression of NADPH Oxidase Activity May Slow the Expansion of Osteolytic Bone Metastases. Healthcare. 2016; 4(3):60.Chicago/Turabian Style
McCarty, Mark F.; DiNicolantonio, James. 2016. "Suppression of NADPH Oxidase Activity May Slow the Expansion of Osteolytic Bone Metastases." Healthcare 4, no. 3: 60.
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.