Bcl‐2 mediated modulation of vascularization in prostate cancer xenografts

Sakai, Yoshihisa; Goodison, Steve; Kusmartsev, Sergei; Fletcher, Bradley S.; Eruslanov, Evgeniy; Cao, Wengang; Porvasnik, Stacy; Namiki, Kazunori; Anai, Satoshi; Rosser, Charles J.

doi:10.1002/pros.20888

Cited by 16 publications

(12 citation statements)

References 45 publications

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“…In vitro studies indicate that TEM8 has a role in various endothelial cell functions (4)(5)(6) and the extracellular domain of TEM8 can bind to extracellular matrix proteins (4, 7) as well as the protective antigen of anthrax toxin (8). Expression profiles for TEM8 include both research and clinical samples that provide strong evidence for the increased expression of TEM8 in tumor endothelial cells (3,7,9). In normal adult tissues, TEM8 expression is sporadic and found at lower levels than in tumor endothelium (7,10).…”

Section: Introductionmentioning

confidence: 99%

Targeting Tumor Endothelial Marker 8 in the Tumor Vasculature of Colorectal Carcinomas in Mice

Fernando

Fletcher²

2009

Cancer Research

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Tumor endothelial marker 8 (TEM8) is a recently described protein that is preferentially expressed within tumor endothelium. We have developed a fusion protein that targets TEM8 and disrupts tumor vasculature by promoting localized thrombosis. Fusion protein specificity and function were evaluated using Western blot analysis, ELISA, and enzymatic assays. A xenograft model of colorectal carcinoma was used to test the efficacy of targeted and control fusion proteins. Mice treated with the gene encoding anti-TEM8/truncated tissue factor exhibited a 53% reduction in tumor volume when compared with the untreated animals (P < 0.0001; n = 10) and achieved a 49% increase in tumor growth delay by Kaplan-Meier analysis (P = 0.0367; n = 6). Immunohistochemistry confirmed tumor endothelial expression of TEM8, fusion protein homing to tumor vasculature, decrease in vessel density, and localized areas of thrombosis. These data support the hypothesis that targeting TEM8 can be an effective approach to influence tumor development by disrupting tumor vasculature. [Cancer Res 2009;69(12):5126-32]

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Section: Introductionmentioning

confidence: 99%

Targeting Tumor Endothelial Marker 8 in the Tumor Vasculature of Colorectal Carcinomas in Mice

Fernando

Fletcher²

2009

Cancer Research

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“…The increased angiogenic potential correlated with increased serum levels of basic FGF (bFGF), IL-8 and MMP-9. 20 Subsequently, we evaluated human endothelial cells (human umbilical vein endothelial cells (HUVEC) and human dermal microvascular endothelial cells (HDMECs)) cultured in conditioned media from Bcl-2-overexpressing human prostate cancer cells. The conditioned media induced increased rates of proliferation and the expression of important antiapoptotic genes/proteins, possibly providing a survival advantage over endothelial cells grown in conditioned media from cancer cells with low Bcl-2 expression.…”

mentioning

confidence: 99%

Expression of CXCL1 in human endothelial cells induces angiogenesis through the CXCR2 receptor and the ERK1/2 and EGF pathways

Miyake¹,

Goodison

Urquidi³

et al. 2013

Laboratory Investigation

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119

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Endothelial cell growth and proliferation are critical for angiogenesis; thus, greater insight into the regulation of pathological angiogenesis is greatly needed. Previous studies have reported on chemokine (C-X-C motif) ligand 1 (CXCL1) expression in epithelial cells and that secretion of CXCL1 from these epithelial cells induces angiogenesis. However, limited reports have demonstrated CXCL1 expression in endothelial cells. In this report, we present data that expand on the role of CXCL1 in human endothelial cells inducing angiogenesis. Specifically, CXCL1 is expressed and secreted from human endothelial cells. Interference of CXCL1 function using neutralizing antibodies resulted in a reduction in endothelial cell migration and viability/proliferation, the latter associated with a decrease in levels of cyclin D and cdk4. In vitro studies revealed that CXCL1 influenced neoangiogenesis through the regulation of epidermal growth factor and ERK1/2. In a xenograft angiogenesis model, interference of CXCL1 function resulted in inhibition of angiogenesis. A better understanding of the role of CXCL1 in the interactions between the endothelial and epithelial components will provide insight into how human tissues use CXCL1 to survive and thrive in a hostile environment.

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“…The positive effect of the overexpression on mTORC1 activity indicates that up-regulation of these antiapoptotic proteins not only enhances cell survival but also stimulates mTOR-dependent proliferation in cancer cells. In support of this notion, it was found that up-regulation of Bcl-2 increased tumor cell proliferation and vascularization in prostate cancer xenografts (20), two events under control of mTORC1. Because translation of Bcl-2 and Bcl-X L is regulated by mTORC1-dependent activation of eIF4E (8), an enhanced mTORC1 activity is expected to increase the production of the two antiapoptotic proteins, which in turn is anticipated to further stimulate mTORC1 activity through the cross-talk.…”

Section: Discussionmentioning

confidence: 83%

Regulation of Mammalian Target of Rapamycin Complex 1 by Bcl-2 and Bcl-XL Proteins

Zou¹,

Lai²,

Zhao³

et al. 2013

Journal of Biological Chemistry

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Background: mTORC1 is a protein kinase that plays a central role in cell growth and metabolism. Results: mTORC1 signaling activity is affected by expression levels of two apoptotic proteins, Bcl-2 and Bcl-X L . Conclusion: Bcl-2 and Bcl-X L control mTORC1 activity by affecting the binding of mTORC1 with its inhibitor FKBP38. Significance: The novel cross-talk between Bcl-2/X L and mTORC1 signaling is likely to play an important role in cancer development.

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Bcl‐2 mediated modulation of vascularization in prostate cancer xenografts

Cited by 16 publications

References 45 publications

Targeting Tumor Endothelial Marker 8 in the Tumor Vasculature of Colorectal Carcinomas in Mice

Targeting Tumor Endothelial Marker 8 in the Tumor Vasculature of Colorectal Carcinomas in Mice

Expression of CXCL1 in human endothelial cells induces angiogenesis through the CXCR2 receptor and the ERK1/2 and EGF pathways

Regulation of Mammalian Target of Rapamycin Complex 1 by Bcl-2 and Bcl-XL Proteins

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