Molecular Regulation of Bone Marrow Metastasis in Prostate and Breast Cancer

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It has been shown that platelets, which are transient cells in BM microenvironment, are important for metastasis of a variety of solid tumors (Figure 1). Platelets bind circulating tumor cells, protecting them against anoikis (a type of programmed cell death occurring due to detachment of the cell from surrounding ECM) as well as against the innate immune system (2, 56, 57). Platelet-derived TGF-β and direct contact between platelets and tumor cells synergistically activate TGF-β/Smad and NF-κB pathways, leading to epithelial-mesenchymal transition (EMT), increased invasion and metastasis (58). In addition, during platelet aggregation by breast cancer cells, platelet-derived lysophosphatidic acid (LPA) induces the release of IL-6 and IL-8 from breast cancer cells, which eventually lead to osteoclastic activation and bone resorption (59). Megakaryocyte ploidy is significantly higher in patients with metastatic disease. Megakaryocyte/platelet surface integrin αIIb/β3 may be involved in tumor colonization in bone marrow, since the mice lacking β3 integrin or those receiving αIIb/β3 inhibitors are protected against bone metastases (60).
MiRNAs and BM metastasis
MiRNA are small 19-22 nucleotide RNA molecules involved in regulation of processes such as proliferation and apoptosis (61). Altered expression of miRNAs has been found to affect the mentioned cellular processes, and may be directly related with cancer development and progression, ultimately resulting in metastasis (62). MiRNA have been recognized as activators (metastamir) or suppressors of metastasis progression, and they are involved in various stages of metastasis (63) (Table 2). The expression of miR-16 in human PCa is decreased compared with normal prostate tissues, and e...

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