Sequential development of an angiogenic phenotype by human fibroblasts progressing to tumorigenicity

Volpert, Olga V.; Dameron, Kristina M.; Bouck, Noël

doi:10.1038/sj.onc.1200977

Cited by 177 publications

(113 citation statements)

References 15 publications

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“…This study showed that stromal angiogenesis is finely controlled by TSP-2 as well as VEGF-189 expression, and that TSP-2 expression is of prognostic significance in colon cancer. Angiogenic phenotype which may be able to support tumorigenicity can arise in a stepwise fashion in response to both a decrease in the secretion of inhibitors and the sequential upregulation of the secretion of inducers of angiogenesis (Volpert et al, 1997). The close correlation and local balance between tissue stable TSP-2 and cell-associated VEGF-189 shown in this study are critical for the progression of colon cancer.…”

Section: Discussionmentioning

confidence: 88%

Thrombospondin 2 expression is correlated with inhibition of angiogenesis and metastasis of colon cancer

et al. 1998

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Summary Two subtypes of thrombospondin (TSP-1 and TSP-2) have inhibitory roles in angiogenesis in vitro, although the biological significance of these TSP isoforms has not been determined in vivo. We examined TSP-1 and TSP-2 gene expression by reverse transcription polymerase chain reaction (RT-PCR) analysis in 61 colon cancers. Thirty-eight of these 61 colon cancers were positive for TSP-2 expression and showed hepatic metastasis at a significantly lower incidence than those without TSP-2 expression (P = 0.02). TSP-2 expression was significantly associated with M0 stage in these colon cancers (P = 0.03), whereas TSP-1 expression showed no apparent correlation with these factors. The colon cancer patients with TSP-2 expression showed a significantly low frequency of liver metastasis correlated with the cell-associated isoform of vascular endothelial growth factor (VEGF-189) (P = 0.0006). Vascularity was estimated by CD34 staining, and TSP-2(-)/VEGF-189(+) colon cancers showed significantly increased vessel counts and density in the stroma (P < 0.0001). TSP-2(-)/VEGF-189(+) colon cancer patients also showed significantly poorer prognosis compared with those with TSP-2(+) / VEGF-189(-) (P = 0.0014). These results suggest that colon cancer metastasis is critically determined by angiogenesis resulting from the balance between the angioinhibitory factor TSP-2 and angiogenic factor VEGF-189.

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Section: Discussionmentioning

confidence: 88%

Thrombospondin 2 expression is correlated with inhibition of angiogenesis and metastasis of colon cancer

et al. 1998

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“…58 p53 has been shown to transcriptionally regulate many of these angiogenic and antiangiogenic factors. 12 In addition, Volpert et al 59 demonstrated that the development of the angiogenic phenotype in human fibroblasts occurs in a stepwise fashion and was dependent upon loss of both alleles of wtp53. Thus, restoration of wtp53 function in tumor cells could lead to inhibition of angiogenesis.…”

Section: Discussionmentioning

confidence: 99%

Downmodulation of bFGF-binding protein expression following restoration of p53 function

et al. 2001

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Angiogenesis is a requirement for solid tumor growth. Therefore, inhibition of this neovascularization is one mechanism by which restoration of wtp53 function may lead to tumor regression. Here we report that adenoviral vector -mediated wild -type p53 transduction results in growth inhibition of squamous cell carcinoma of the head and neck tumor cells both in vitro and in a xenograft mouse model. This growth inhibition is associated with the down -regulation of the expression of fibroblast growth factor binding protein, a secreted protein required for the activation of angiogenic factor basic FGF. These findings suggest that wtp53 -induced tumor regression is due, at least in part, to antiangiogenesis mediated by the downmodulation of fibroblast growth factor binding protein. Cancer Gene Therapy ( 2001 ) 8, 771 -782

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“…These results provide the ®rst indication that E6 viral oncoprotein induces VEGF gene expression by promoter transcriptional activation. Direct induction of VEGF expression by HPV-16 E6 oncoprotein could co-operate with other genetic alterations and/or microenvironmental changes such as hypoxia (Ravi et al, 2000) to result in maximal elevations of VEGF expression, similar to the co-operative e ects of hypoxia and other oncogenes, or combinations of activated oncogenes and mutant suppressor genes (Volpert et al, 1997) in inducing maximal upregulation of VEGF expression (Mazure et al, 1996). Thus blockade of E6 expression or function could conceivably result in indirect suppression of cervical cancer growth in vivo through a mechanism involving downregulation of VEGF-mediated angiogenesis.…”

Section: Hpv-16 E6 Oncoprotein and Vegf In Tumor Angiogenesismentioning

confidence: 99%

Oncogenes and tumor angiogenesis: the HPV-16 E6 oncoprotein activates the vascular endothelial growth factor (VEGF) gene promoter in a p53 independent manner

et al. 2000

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Sequential development of an angiogenic phenotype by human fibroblasts progressing to tumorigenicity

Cited by 177 publications

References 15 publications

Thrombospondin 2 expression is correlated with inhibition of angiogenesis and metastasis of colon cancer

Thrombospondin 2 expression is correlated with inhibition of angiogenesis and metastasis of colon cancer

Downmodulation of bFGF-binding protein expression following restoration of p53 function

Oncogenes and tumor angiogenesis: the HPV-16 E6 oncoprotein activates the vascular endothelial growth factor (VEGF) gene promoter in a p53 independent manner

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