title: 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.
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.affiliation: 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.
authors.forename: Raffaella
authors.initials: R
authors.lastname: Giannice
authors.forename: Marco
authors.initials: M
authors.lastname: Erreni
authors.forename: Paola
authors.initials: P
authors.lastname: Allavena
authors.forename: Mauro
authors.initials: M
authors.lastname: Buscaglia
authors.forename: Roberto
authors.initials: R
authors.lastname: Tozzi
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D054371:Chemokine CXCL11 / Q000235:genetics / Q000378:metabolism; D054377:Chemokine CXCL12 / Q000235:genetics / Q000378:metabolism; D018925:Chemokines / Q000235:genetics* / Q000378:metabolism; D016889:Endometrial Neoplasms / Q000235:genetics* / Q000473:pathology; D004717:Endometrium / Q000378:metabolism* / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D016209:Interleukin-8 / Q000235:genetics / Q000378:metabolism; D019746:Intramolecular Oxidoreductases / Q000235:genetics* / Q000378:metabolism; D008263:Macrophage Migration-Inhibitory Factors / Q000235:genetics* / Q000378:metabolism; D008875:Middle Aged; D010865:Pilot Projects; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D019718:Receptors, CXCR4 / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D059016:Tumor Microenvironment / Q000235:genetics*; D042461:Vascular Endothelial Growth Factor A / Q000235:genetics* / Q000378:metabolism
chemical_list: C515202:CXCL11 protein, human; C515255:CXCL12 protein, human; C508606:CXCL8 protein, human; C527276:CXCR4 protein, human; D054371:Chemokine CXCL11; D054377:Chemokine CXCL12; D018925:Chemokines; D016209:Interleukin-8; D008263:Macrophage Migration-Inhibitory Factors; D012333:RNA, Messenger; D019718:Receptors, CXCR4; C467484:VEGFA protein, human; D042461:Vascular Endothelial Growth Factor A; D019746:Intramolecular Oxidoreductases; C515598:MIF protein, human
keywords: Chemokines; EC; Endometrial cancer; MIF; Macrophage Migration Inhibitory Factor; NE; NSLCC; PGK; TAMs; Tumor Associated Macrophages; Tumor microenvironment; VEGF; Vascular Endothelial Growth Factor; endometrial cancer; normal endometrium; not small lung cancer cell; phosphoglycerate kinase