Implication of vascular endothelial growth factor and p53 status for angiogenesis in noninvasive colorectal carcinoma

Kondo, Yoko; Arii, Shigeki; Furutani, Masaharu; Isigami, Shun-Ichi; Mori, Akira; Onodera, Hisashi; Chiba, Tsutomu; Imamura, Masayuki

doi:10.1002/(sici)1097-0142(20000415)88:8<1820::aid-cncr10>3.0.co;2-5

Cited by 61 publications

(26 citation statements)

References 21 publications

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“…After exclusion of the references which were out of the scope of our meta-analysis, there remained 45 studies dealing with MVD (see Appendix B) and 27 dealing with VEGF expression (see Appendix C), representing a total of 56 independent studies. Some of these articles did not fulfil our inclusion criteria (mainly because they did not mention survival data), six for MVD (Vermeulen et al, 1995;Banner et al, 1998;Nanashima et al, 1998;Kondo et al, 2000;Barozzi et al, 2002;Saad et al, 2004) and five for VEGF (Nanashima et al, 1998;Kondo et al, 2000;Seto et al, 2000;Barozzi et al, 2002;Saad et al, 2004). One study was written in Chinese language, with an English abstract and did not seem to mention survival data (Liu et al, 1999).…”

Section: Resultsmentioning

confidence: 99%

Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature

et al. 2006

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We performed a meta-analysis of all published studies relating intratumoural microvessel density (MVD) (45 studies) or vascular endothelial growth factor (VEGF) expression (27 studies), both reflecting angiogenesis, to relapse free (RFS) and overall survival (OS) in colorectal cancer (CRC). For each study, MVD impact was measured by risk ratio between the two survival distributions with median MVD as cutoff. Eleven studies did not mention survival data or fit inclusion criteria, six were multiple publications of same series, leaving 32 independent studies for MVD (3496 patients) and 18 for VEGF (2050 patients). Microvessel density was assessed by immunohistochemistry, using antibodies against factor VIII (16 studies), CD31 (10 studies) or CD34 (seven studies). Vascular endothelial growth factor expression was mostly assessed by immunohistochemistry. Statistics were performed for MVD in 22 studies (the others lacking survival statistics) including nine studies (n ¼ 957) for RFS and 18 for OS (n ¼ 2383) and for VEGF in 17 studies, including nine studies for RFS (n ¼ 1064) and 10 for OS (n ¼ 1301). High MVD significantly predicted poor RFS (RR ¼ 2.32 95% CI: 1.39 -3.90; Po0.001) and OS (RR ¼ 1.44; 95% CI: 1.08 -1.92; P ¼ 0.01). Using CD31 or CD34, MVD was inversely related to survival, whereas it was not using factor VIII. Vascular endothelial growth factor expression significantly predicted poor RFS (RR ¼ 2.84; 95% CI: 1.95 -4.16) and OS (RR ¼ 1.65; 95% CI: 1.27 -2.14). To strengthen our findings, future prospective studies should explore the relation between MVD or VEGF expression and survival or response to therapy (e.g. antiangiogenic therapy). Assessment of these angiogenic markers should be better standardised in future studies.

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Section: Resultsmentioning

confidence: 99%

Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature

et al. 2006

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“…VEGF induction is associated with increases in microvascular density, which in turn is directly correlated with increased metastasis of many cancers, including colorectal cancer (45). For example, colonic VEGF induction is correlated with tumor angiogenesis (46), tumor progression (47), and metastatic potential, particularly to the liver in individuals with colorectal cancers (48). Similarly, serum VEGF levels are higher in patients with advanced colorectal cancers relative to healthy volunteers (49)(50)(51)(52).…”

Section: R E S E a R C H A R T I C L E M O L M Ementioning

confidence: 99%

Macrophage Migration Inhibitory Factor Promotes Colorectal Cancer

Chen

Yang

et al. 2009

Mol Med

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A growing body of evidence implicates macrophage migration inhibitory factor (MIF) in tumorigenesis and metastasis. In this study, we investigated whether MIF expression was associated with clinicopathologic features of colorectal carcinoma (CRC), especially in tumors with hepatic metastasis, and whether neutralization of endogenous MIF using anti-MIF therapeutics would inhibit tumor growth and/or decrease the frequency of colorectal hepatic metastases in a mouse colon carcinoma model. The concentration of serum MIF was positively correlated with an increased risk of hepatic metastasis in human patients with CRC (R = 1.25, 95% confidence internal = 1.02-1.52, P = 0.03). MIF was also dramatically upregulated in human colorectal tissue, with 20-40 times as many MIF-positive cells found in the mucosa of patients with CRC than in normal tissue (P < 0.001 ANOVA). Moreover, in those patients with metastatic colorectal cancer in the liver, MIF-positive cells were similarly increased in the diseased hepatic tissue. This increased MIF expression was restricted to diseased tissue and not found in areas of the liver with normal morphology. In subsequent in vitro experiments, we found that addition of recombinant MIF to colonic cell lines significantly increased their invasive properties and the expression of several genes (for example, matrix metalloproteinase 9 and vascular endothelial growth factor) known to be upregulated in cancerous tissue. Finally, we treated mice that had been given CT26 colon carcinoma cell transplants with anti-MIF therapeutics-either the MIF-specific inhibitor ISO-1 or neutralizing anti-MIF antibodies-and observed a significant reduction in tumor burden relative to vehicle-treated animals. Taken together, these data demonstrate that MIF expression was not only correlated with the presence of colorectal cancer but also may play a direct role in cancer development.

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“…VEGF mRNA levels are closely correlated with tumor angiogenesis (Asano et al, 1995;Zhang et al, 1995;Cheng et al, 1996;Saleh et al, 1996;Mori et al, 1999;Kondo et al, 2000;Ho¨pfl et al, 2002). Transfection of the gene for VEGF into tumor cells such as breast carcinoma cells (Zhang et al, 1995), fibrosarcoma cells (Mori et al, 1999) and colon carcinoma cells (Kondo et al, 2000) resulted in increases in vascularization and in vivo growth rate. Conversely, expression of VEGF antisense or neutralizing anti-VEGF antibody led to retarded growth of glioblastomas in vivo (Asano et al, 1995;Cheng et al, 1996;Saleh et al, 1996).…”

Section: Introductionmentioning

confidence: 99%

Constitutive upregulation of hypoxia-inducible factor-1α mRNA occurring in highly metastatic lung carcinoma cells leads to vascular endothelial growth factor overexpression upon hypoxic exposure

et al. 2003

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Neoangiogenesis is crucial for tumor growth and metastasis and is regulated by various angiogenic factors including vascular endothelial growth factor (VEGF). However, little is known whether highly metastatic cells express higher level of VEGF in response to various stimuli, thereby increasing neoangiogenesis compared to low-metastatic cells. Here we report that hypoxia markedly induced the expression of VEGF mRNA in the cell lines with high-metastatic potential (A11 and D6 cells) compared to the cell lines with low-metastatic potential (P29 and P34 cells) established from Lewis lung carcinoma. A11 cells exhibited higher VEGF genepromoter activity, produced a larger amount of VEGF and showed higher activity to induce neoangiogenesis than P29 cells. Although the degradation rate of VEGF mRNA under hypoxic conditions was similar in both cell lines, hypoxia-inducible factor-1a (HIF-1a) mRNA, but not HIF-1b mRNA, was found to be constitutively upregulated in A11 cells compared to P29 cells. Accordingly, the level of HIF-1a protein in response to hypoxia was higher in A11 cells than in P29 cells. Upregulation of HIF-1a mRNA was also observed in D6 cells but not in P34 cells. Thus, the high-metastatic cells produced a larger amount of VEGF under hypoxic conditions through constitutive HIF-1a mRNA upregulation compared to the low-metastatic cells, thereby leading to extensive neoangiogenesis.

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Implication of vascular endothelial growth factor and p53 status for angiogenesis in noninvasive colorectal carcinoma

Cited by 61 publications

References 21 publications

Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature

Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature

Macrophage Migration Inhibitory Factor Promotes Colorectal Cancer

Constitutive upregulation of hypoxia-inducible factor-1α mRNA occurring in highly metastatic lung carcinoma cells leads to vascular endothelial growth factor overexpression upon hypoxic exposure

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