The Role of Vascular Endothelial Growth Factor in Metastatic Prostate Cancer to the Skeleton

Roberts, Emma A.; Cossigny, D. A.; Quan, Gerald M. Y.

doi:10.1155/2013/418340

Cited by 101 publications

(84 citation statements)

References 86 publications

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“…VEGF has been shown to play pivotal roles in the regulation of normal and pathogenesis‐related angiogenesis. Among the three VEGF receptors (VEGFR1, 2 and 3), VEGFR2 is generally accepted as the major mediator of VEGF‐driven responses in tumor progression . ENZ treatment alone led to reduced VEGF secretion compared to control treatment in VCaP cells ( p < 0.001), but not in C4‐2B cells.…”

Section: Resultsmentioning

confidence: 99%

Enzalutamide and CXCR7 inhibitor combination treatment suppresses cell growth and angiogenic signaling in castration‐resistant prostate cancer models

Luo

Azad

Karanika

et al. 2018

Intl Journal of Cancer

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Previous studies have shown that increased levels of chemokine receptor CXCR7 are associated with the increased invasiveness of prostate cancer cells. We now show that CXCR7 expression is upregulated in VCaP and C4‐2B cells after enzalutamide (ENZ) treatment. ENZ treatment induced apoptosis (sub‐G1) in VCaP and C4‐2B cells, and this effect was further increased after combination treatment with ENZ and CCX771, a specific CXCR7 inhibitor. The levels of p‐EGFR (Y1068), p‐AKT (T308) and VEGFR2 were reduced after ENZ and CCX771 combination treatment compared to single agent treatment. In addition, significantly greater reductions in migration were shown after combination treatment compared to those of single agents or vehicle controls, and importantly, similar reductions in the levels of secreted VEGF were also demonstrated. Orthotopic VCaP xenograft growth and subcutaneous MDA133‐4 patient‐derived xenograft (PDX) tumor growth was reduced by single agent treatment, but significantly greater suppression was observed in the combination treatment group. Although overall microvessel densities in the tumor tissues were not different among the different treatment groups, a significant reduction in large blood vessels (>100 μm2) was observed in tumors following combination treatment. Apoptotic indices in tumor tissues were significantly increased following combination treatment compared with vehicle control‐treated tumor tissues. Our results demonstrate that significant tumor suppression mediated by ENZ and CXCR7 combination treatment may be due, in part, to reductions in proangiogenic signaling and in the formation of large blood vessels in prostate cancer tumors.

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Section: Resultsmentioning

confidence: 99%

Enzalutamide and CXCR7 inhibitor combination treatment suppresses cell growth and angiogenic signaling in castration‐resistant prostate cancer models

Luo

Azad

Karanika

et al. 2018

Intl Journal of Cancer

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“…For example, vascular endothelial growth factor (VEGF) stimulates angiogenesis and has also been implicated in promoting metastasis [101]. Fibroblast growth factors (FGFs) signal via mitogen-activated protein kinases (MAPK) to drive proliferation while also promoting angiogenesis, and in some contexts terminal differentiation [102].…”

Section: Box 1: Synthesis and Modification Of Hspgsmentioning

confidence: 99%

Heparan sulfate signaling in cancer

Knelson

Nee

Blobe

2014

Trends in Biochemical Sciences

167

168

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Summary Heparan sulfate (HS) is a biopolymer consisting of variably sulfated repeating disaccharide units. The anticoagulant heparin is a highly sulfated intracellular variant of HS. HS has demonstrated roles in embryonic development, homeostasis, and human disease via non-covalent interactions with numerous cellular proteins, including growth factors and their receptors. HS can function as a co-receptor by enhancing receptor-complex formation. In other contexts, HS disrupts signaling complexes or serves as a ligand sink. The effects of HS on growth factor signaling are tightly regulated by the actions of sulfyltransferases, sulfatases and heparanases. HS has important emerging roles in oncogenesis and heparin derivatives represent potential therapeutic strategies for human cancers. Here we review recent insights into HS signaling in tumor proliferation, angiogenesis, metastasis, and differentiation. A cancer-specific understanding of HS signaling could uncover potential therapeutic targets in this highly actionable signaling network.

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“…The Figure 5A). The VEGF is highly expressed in prostate cancer cells and it is a well-known stimulator of angiogenesis, and contributes to the distribution of prostate tumor cells to the skeleton or other tissues (Roberts et al, 2013). The mRNA expression of VEGF was slightly lowered in PPC-1 cells after treatment whereas the treated TSU-Pr1 cells displayed a strong increase in the mRNA levels of VEGF ( Figure 5B).…”

Section: Vegf and P21 Expression In Axitinib And Dasatinib Treated Ppmentioning

confidence: 98%

Combination of axitinib and dasatinib for anti-cancer activities in two prostate cancer cell lines

Peng

Liu

Wang³

et al. 2015

Bangladesh J Pharmacol

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<p class="Abstract">Prostate cancer is major cause of cancer related deaths worldwide in men. There are new treatment methods and drugs are being developed with promising results in two of the prostate cancer cell lines (PPC-1 and TSU-Pr1). These two cells were treated with 20 uM of axitinib combined with dasatinib for 6-72 hours. The cell viability assessed by the cytotoxicity assay. Various regulatory genes such as c-KIT, cell cycle and apoptosis and angiogenic factors were also studied. The enzyme activity of apoptosis efector caspase-3 was colorimetrically determined. Axitinib and dasatinib combination lowered the survival rate of PPC-1 cells but enhanced the survival rate of TSU-Pr1 cells. The protein expression levels in apoptosis and angiogenesis factors were also found to be in contrast between the two cell lines. PPC-1 and TSU-Pr1 cells displayed a different response to axitinib with dasatinib, which explains different expression levels of regulators of cell-cycle, apoptosis and angiogenesis.</p><p> </p>

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The Role of Vascular Endothelial Growth Factor in Metastatic Prostate Cancer to the Skeleton

Cited by 101 publications

References 86 publications

Enzalutamide and CXCR7 inhibitor combination treatment suppresses cell growth and angiogenic signaling in castration‐resistant prostate cancer models

Enzalutamide and CXCR7 inhibitor combination treatment suppresses cell growth and angiogenic signaling in castration‐resistant prostate cancer models

Heparan sulfate signaling in cancer

Combination of axitinib and dasatinib for anti-cancer activities in two prostate cancer cell lines

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