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Chemokines mRNA expression in relation to the Macrophage Migration Inhibitory Factor (MIF) mRNA and Vascular Endothelial Growth Factor (VEGF) mRNA expression in the microenvironment of endometrial cancer tissue and normal endometrium: a pilot study.
Cytokine 2013; 64(2):509-15C

Abstract

Tumor microenvironment inflammatory cells play a major role in cancer progression. Among these, the Tumor Associated Macrophages (TAMs) infiltration depends on the kind of chemokine, cytokines and growth factors secreted by the tumor cells and by the stroma in response to the cancer invasion. TAMs have been found to promote anti-tumor response in early stages and to stimulate neovascularization and metastases in advanced disease. In the microenvironment chemo-attractants of many human cancers, MIF and VEGF correlate with an increased TAMs recruitment. In addition, MIF enhances tumor cells metastases by modulating the immune responses and by promoting the angiogenesis related to VEGF. On the contrary the inhibition of MIF can lead to cell cycle arrest and apoptosis. Some chemokines (e.g. CXCL12, CXCL11, CXCL8) and their receptors, thanks to their ability to modulate migration and proliferation, are involved in the angiogenetic process. In this study we compared the expression of MIF mRNA with VEGF mRNA expression and with mRNA expression of other chemokines related to neo-angiogenesis, such as CXCL12, CXCL11, CXCL8 and CXCR4, in human endometrial cancer tissue (EC) and normal endometrium (NE). Fresh samples of EC tissue and NE were extracted from 15 patients with FIGO stage I-III undergoing primary surgery. Some of the tissue was sent for histology and part of it was treated with RNA later and stored at -80°C. Four patients dropped out. A significant up-regulation of MIF mRNA in EC tissue versus NE samples (P=0.01) was observed in all 11 patients. The MIF mRNA over-expression was coincident with a VEGF mRNA overexpression in 54% of patients (P=NS). MIF mRNA was inversely related to CXCL12 mRNA expression (P=0.01). MIF over-expression was significantly related to low grading G1-2 (P=0.01), endometrial type I (P=0.05), no lymphovascular spaces invasion (P=0.01) and 3years DFS (P=0.01). As reported in previous studies on patients with breast cancer, our data suggest that the up-regulation of MIF in patients with endometrial cancer might be related to the inhibition of distant and lymphatic spread.

Authors+Show Affiliations

Churchill Cancer Centre, Gynecologic Oncology Department, Old Road, Headington, Oxford OX3 7LE, UK; S. Carlo Borromeo's Hospital, Gynecologic and Obstetrics Department, Via Pio II n. 3, 20153 MI, Italy; Immunology and Inflammation Department, IRCCS Humanitas, Via A. Manzoni 53, Rozzano, MI, Italy. Electronic address: Raffaellagiannice@libero.it.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

23985752

Citation

Giannice, Raffaella, et al. "Chemokines mRNA Expression in Relation to the Macrophage Migration Inhibitory Factor (MIF) mRNA and Vascular Endothelial Growth Factor (VEGF) mRNA Expression in the Microenvironment of Endometrial Cancer Tissue and Normal Endometrium: a Pilot Study." Cytokine, vol. 64, no. 2, 2013, pp. 509-15.
Giannice R, Erreni M, Allavena P, et al. Chemokines mRNA expression in relation to the Macrophage Migration Inhibitory Factor (MIF) mRNA and Vascular Endothelial Growth Factor (VEGF) mRNA expression in the microenvironment of endometrial cancer tissue and normal endometrium: a pilot study. Cytokine. 2013;64(2):509-15.
Giannice, R., Erreni, M., Allavena, P., Buscaglia, M., & Tozzi, R. (2013). Chemokines mRNA expression in relation to the Macrophage Migration Inhibitory Factor (MIF) mRNA and Vascular Endothelial Growth Factor (VEGF) mRNA expression in the microenvironment of endometrial cancer tissue and normal endometrium: a pilot study. Cytokine, 64(2), pp. 509-15. doi:10.1016/j.cyto.2013.07.024.
Giannice R, et al. Chemokines mRNA Expression in Relation to the Macrophage Migration Inhibitory Factor (MIF) mRNA and Vascular Endothelial Growth Factor (VEGF) mRNA Expression in the Microenvironment of Endometrial Cancer Tissue and Normal Endometrium: a Pilot Study. Cytokine. 2013;64(2):509-15. PubMed PMID: 23985752.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Chemokines mRNA expression in relation to the Macrophage Migration Inhibitory Factor (MIF) mRNA and Vascular Endothelial Growth Factor (VEGF) mRNA expression in the microenvironment of endometrial cancer tissue and normal endometrium: a pilot study. AU - Giannice,Raffaella, AU - Erreni,Marco, AU - Allavena,Paola, AU - Buscaglia,Mauro, AU - Tozzi,Roberto, Y1 - 2013/08/25/ PY - 2012/12/16/received PY - 2013/07/03/revised PY - 2013/07/21/accepted PY - 2013/8/30/entrez PY - 2013/8/30/pubmed PY - 2014/5/8/medline KW - Chemokines KW - EC KW - Endometrial cancer KW - MIF KW - Macrophage Migration Inhibitory Factor KW - NE KW - NSLCC KW - PGK KW - TAMs KW - Tumor Associated Macrophages KW - Tumor microenvironment KW - VEGF KW - Vascular Endothelial Growth Factor KW - endometrial cancer KW - normal endometrium KW - not small lung cancer cell KW - phosphoglycerate kinase SP - 509 EP - 15 JF - Cytokine JO - Cytokine VL - 64 IS - 2 N2 - Tumor microenvironment inflammatory cells play a major role in cancer progression. Among these, the Tumor Associated Macrophages (TAMs) infiltration depends on the kind of chemokine, cytokines and growth factors secreted by the tumor cells and by the stroma in response to the cancer invasion. TAMs have been found to promote anti-tumor response in early stages and to stimulate neovascularization and metastases in advanced disease. In the microenvironment chemo-attractants of many human cancers, MIF and VEGF correlate with an increased TAMs recruitment. In addition, MIF enhances tumor cells metastases by modulating the immune responses and by promoting the angiogenesis related to VEGF. On the contrary the inhibition of MIF can lead to cell cycle arrest and apoptosis. Some chemokines (e.g. CXCL12, CXCL11, CXCL8) and their receptors, thanks to their ability to modulate migration and proliferation, are involved in the angiogenetic process. In this study we compared the expression of MIF mRNA with VEGF mRNA expression and with mRNA expression of other chemokines related to neo-angiogenesis, such as CXCL12, CXCL11, CXCL8 and CXCR4, in human endometrial cancer tissue (EC) and normal endometrium (NE). Fresh samples of EC tissue and NE were extracted from 15 patients with FIGO stage I-III undergoing primary surgery. Some of the tissue was sent for histology and part of it was treated with RNA later and stored at -80°C. Four patients dropped out. A significant up-regulation of MIF mRNA in EC tissue versus NE samples (P=0.01) was observed in all 11 patients. The MIF mRNA over-expression was coincident with a VEGF mRNA overexpression in 54% of patients (P=NS). MIF mRNA was inversely related to CXCL12 mRNA expression (P=0.01). MIF over-expression was significantly related to low grading G1-2 (P=0.01), endometrial type I (P=0.05), no lymphovascular spaces invasion (P=0.01) and 3years DFS (P=0.01). As reported in previous studies on patients with breast cancer, our data suggest that the up-regulation of MIF in patients with endometrial cancer might be related to the inhibition of distant and lymphatic spread. SN - 1096-0023 UR - https://www.unboundmedicine.com/medline/citation/23985752/Chemokines_mRNA_expression_in_relation_to_the_Macrophage_Migration_Inhibitory_Factor__MIF__mRNA_and_Vascular_Endothelial_Growth_Factor__VEGF__mRNA_expression_in_the_microenvironment_of_endometrial_cancer_tissue_and_normal_endometrium:_a_pilot_study_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S1043-4666(13)00640-6 DB - PRIME DP - Unbound Medicine ER -