Bone metastases can lead to pain, pathological fractures, nerve c

Bone metastases can lead to pain, pathological fractures, nerve compression syndromes, and hypercalcemia. Current treatments are mainly palliative. Despite the high incidence and serious consequences of skeletal metastasis of prostate cancer, the mechanism underlying this osteotropism is unclear. However, it is clear that VEGF has been implicated in various carcinogenesis and metastasis as well as in angiogenesis. VEGF is expressed by prostate cancer at a high level [7–9], and its expression correlates with increasing grade, vascularity, and tumorigenicity [9, 10]. These relationships have been observed in human as well

as in animal models of prostate cancer. High VEGF levels in prostate cancer are associated with poor prognosis. In addition, VEGF produced by tumor cells affects bone remodeling and might, therefore, FRAX597 facilitate nesting

of metastatic cells in bone [11]. Bevacizumab is a recombinant, humanized monoclonal antibody that inhibits the binding of vascular endothelial growth factor (VEGF) to its receptors. Several find more experimental studies have examined the extent to which VEGF inhibitors or VEGF targeted agents prevent tumor cell growth and metastasis in vitro and in vivo [12–20]. In this study, we focus on the effect of bevacizumab on human bone metastatic LNCaP-derivative C4-2B prostate cancer cell line. Angiogenesis is one of the critical events required in the cancer metastatic process. VEGF is a specific stimulator of vascular endothelial cell proliferation and tumor angiogenesis. VEGF is produced in response to various cellular and environmental stimuli. VEGF is overexpressed in many human neoplasms [4, Florfenicol 5, 7, 9, 20–22]. This expression is associated with increased tumor size, necrosis and tumor angiogensis. New blood vessels that grow within the tumor secondary to VEGF expression are structurally and functionally irregular, as they exhibit dead ends, disordered blood flow, and increased permeability. These irregularities in blood flow lead to further tumor hypoxia and subsequent increases in VEGF production [23, 24]. In this study, we confirm that human bone

metastatic prostate cancer cell line C4-2B has a higher level of VEGF than its parental cell line LNCaP, although both of cell lines have high levels of VEGF expression. We found that VEGF production significantly increased 6-fold when bone metastatic prostate cancer cells were cocultured with vascular endothelium. VEGF exhibits the effects on the growth and Obeticholic purchase progression of neoplasia. Several studies have shown a correlation between increased VEGF expression and tumor growth [16–23]. Recent studies have indicated that bevacizumab treatment results in a dose-dependent inhibition of tumor growth in vitro and in vivo [18, 24, 25]. In our study, bevacizumab gave a dose-dependent and time-dependent reduction of cell proliferation in human bone metastatic prostate cancer cells. Metastasis is an extraordinarily complex process.

Comments are closed.