Expression of angiogenic regulators, VEGF and leptin, is regulated by the EGF/PI3K/STAT3 pathway in colorectal cancer cells

Cascio, Sandra; Ferla, Rita; D’Andrea, Aleco; Gerbino, Aldo; Bazan, Viviana; Surmacz, Eva; Russo, Antonio

doi:10.1002/jcp.21843

Cited by 47 publications

(31 citation statements)

References 39 publications

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“…The ability to suppress the function of T-cell and NK cells provides the most effective way of identifying MDSCs [96]. The expansion of MDSCs is influenced by pro-myelopoetic factors produced by colorectal carcinoma cells [104], such as stem cell factor (SCF), M-CSF, PGs, IL-6, GM-CSF, and VEGF [105], while the activation factors produced by MDSCs are produced by both activated T-cells and stromal cells and include IFN-γ, TLR ligands, IL-4, IL-13, and TGF-β. The suppressive effect of MDSCs has been associated with the metabolism of L-arginine, a substrate for the two key enzymes, arginase-1 and iNOS (which generates NO).…”

Section: Myeloid-derived Suppressor Cellsmentioning

confidence: 99%

The Tumor Microenvironment in Colorectal Carcinogenesis

Peddareddigari

Wang

DuBois

2010

Cancer Microenvironment

186

163

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Colorectal cancer is the second leading cause of cancer-related mortality in the United States. Therapeutic developments in the past decade have extended life expectancy in patients with metastatic disease. However, metastatic colorectal cancers remain incurable. Numerous agents that were demonstrated to have significant antitumor activity in experimental models translated into disappointing results in extending patient survival. This has resulted in more attention being focused on the contribution of tumor microenvironment to the progression of a number of solid tumors including colorectal cancer. A more complete understanding of interactions between tumor epithelial cells and their stromal elements will enhance therapeutic options and improve clinical outcome. Here we will review the role of various stromal components in colorectal carcinogenesis and discuss the potential of targeting these components for the development of future therapeutic agents.

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Section: Myeloid-derived Suppressor Cellsmentioning

confidence: 99%

The Tumor Microenvironment in Colorectal Carcinogenesis

Peddareddigari

Wang

DuBois

2010

Cancer Microenvironment

186

163

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“…VEGF is believed to be the principal growth stimulatory factor for tumor-related angiogenesis. constitutive activation of Stat3 is able to up-regulate VEGF-a expression in human pancreatic and colorectal cancer cells (12,13).…”

mentioning

confidence: 99%

Significance of CXCR4, phosphorylated STAT3 and VEGF-A expression in resected non-small cell lung cancer

Wang

Chen

Song

et al. 2011

Experimental and Therapeutic Medicine

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Abstract. c-x-c chemokine receptor type 4 (cxcr4) plays an important role in determining the metastatic potential of non-small cell lung cancer. in order to elucidate the effect and mechanism of cxcr4 in tumor angiogenesis we evaluated the clinical significance of CXCR4, phosphorylated signal transducer and activator of transcription 3 (p-Stat3), and vascular endothelial growth factor (VEGF) expression in patients with completely resected non-small cell lung cancer (nSclc). a total of 208 cases of resected nSclc were collected, and expression of cxcr4, p-Stat3 and VEGF-a in tumor tissue was investigated using immunohistochemistry (ihc). We reviewed the patient clinical records to determine the association of the expression of these proteins with the clinical course of the disease. Expression of cxcr4, p-Stat3 and VEGF-a was detected in 56.3, 46.2 and 51.9% of the samples, respectively. We observed co-expression between cxcr4, p-Stat3 and VEGF-a. using multivariate analysis, the expression levels of CXCR4 and VEGF-A were identified as independent prognostic factors that affected overall survival. in conclusion, the results of this study suggest that cxcr4, p-Stat3 and VEGF-a expression may play a role in tumor progression and angiogenesis of nSclc. however, further studies are needed to uncover the detailed mechanism that underlies the role of these proteins in nSclc.

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“…Earlier studies have reported that pSTAT3 promotes tumor angiogenesis by acting as a direct transcriptional activator of VEGF and mediates expression of genes related to tumor growth and metastasis [6]. Recently, Cascio and co-investigators supported this evidence in colon cancer cells by demonstrating the binding of STAT3 to the promoter of VEGF [47]. Elevated levels of MMP-7 mRNA was detected in colorectal tumor tissues with activated form of STAT3 [3].…”

Section: Discussionmentioning

confidence: 93%

Protein Expression of STAT3, pSTAT3, MMP-7 and VEGF in Colorectal Adenocarcinoma: An Immunohistochemical Study

Naidu¹,

Nee²,

Jw³

et al. 2014

JCT

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Background: The purpose of the present study is to investigate the expression levels of STAT3, pSTAT3, MMP-7 and VEGF in colorectal adenocarcinoma, and also to determine association with the clinico-pathological parameters and co-expression of these genes. Methods: An immunohistochemical method was used to evaluate the expression of MMP-7 and VEGF genes in 93 archival tissues whereas STAT3 and pSTAT3 expression was determined in 75 cases. Results: Overexpression of STAT3 was detected in 26.7% (20/75), pSTAT3 in 13.4% (10/75), MMP-7 in 38.8% (36/93) and VEGF in 59.2% (55/93) of the colorectal carcinomas. STAT3, MMP-7 and VEGF immunopositivity were significantly correlated with poorly-differentiated tumors (P = 0.004; P = 0.03; P = 0.002, respectively) but not with other parameters. However, pSTAT3 immunostaining was not significantly associated with the clinico-pathological characteristics. Significant relationship was noted between overexpression of pSTAT3 and STAT3 (P < 0.001), pSTAT3 and VEGF (P = 0.044), pSTAT3 and MMP-7 (P = 0.003), and STAT3 and VEGF (P = 0.037) but marginal association was detected between STAT3 and MMP-7 (P = 0.057), and MMP-7 and VEGF (P = 0.052). Conclusion: Our data suggest that expression of these genes may have an important role in tumor dedifferentiation and may be useful as indicators of biologic aggressiveness. Co-expression of the bio-* Corresponding author. R. Naidu et al. 1176markers by cancer cells may have important implications in colorectal cancer biology and could be useful biological markers of the malignant phenotype.

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Expression of angiogenic regulators, VEGF and leptin, is regulated by the EGF/PI3K/STAT3 pathway in colorectal cancer cells

Cited by 47 publications

References 39 publications

The Tumor Microenvironment in Colorectal Carcinogenesis

The Tumor Microenvironment in Colorectal Carcinogenesis

Significance of CXCR4, phosphorylated STAT3 and VEGF-A expression in resected non-small cell lung cancer

Protein Expression of STAT3, pSTAT3, MMP-7 and VEGF in Colorectal Adenocarcinoma: An Immunohistochemical Study

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