title: Relationship between the inflammatory molecular profile of breast carcinomas and distant metastasis development.
abstract: Inflammatory conditions may promote tumor progression and aggressiveness. In previous reports, we found a group of breast cancer tumors characterized by metalloprotease-11 (MMP-11) expression by intratumoral mononuclear inflammatory cells (MICs), which was associated with distant metastasis development. Thus, in the present study we evaluated the relationship between MMP-11 expression by MICs, distant metastasis development, and a wide panel of inflammatory factors in breast carcinoma. In an initial approach, we analyzed 65 factors associated with tumor progression and inflammation, in a tumor population classified in good or bad prognosis, based on MMP-11 expression by intratumoral MICs. The most differentially expressed factors were then analyzed in a wider tumor population classified according to MMP-11 expression by MICs and also according to metastasis development. These analyses were carried out by Real-time PCR. The results showed that of the 65 starting factors analyzed, those related with MMP-11 expression by MICs were: IL-1, -5, -6, -8, -17, -18, MMP-1, TIMP-1, ADAM-8, -10, -15, -23, ADAMTS-1, -2, -15, Annexin A2, IFNβ, Claudin-3, CCL-3, MyD88, IRAK-4 and NFκB. Of them, factors more differentially expressed between both groups of tumors were IL-1, IL-5, IL-6, IL-17, IFNβ and NFκB. Thereafter, we confirmed in the wider tumor population, that there is a higher expression of those factors in tumors infiltrated by MMP-11 positive MICs. Altogether these results indicate that tumors developing worse prognosis and identified by MMP-11 expression by intratumoral MICs, shows an up-regulation of inflammatory-related genes.
authors.affiliation: Unidad de Investigación, Fundación Hospital de Jove, Gijón, Asturias, Spain.
authors.forename: Noemí
authors.initials: N
authors.lastname: Eiró
authors.forename: Lucía
authors.initials: L
authors.lastname: González
authors.forename: Luis O
authors.initials: LO
authors.lastname: González
authors.forename: Belen
authors.initials: B
authors.lastname: Fernandez-Garcia
authors.forename: Maria Luz
authors.initials: ML
authors.lastname: Lamelas
authors.forename: Laura
authors.initials: L
authors.lastname: Marín
authors.forename: Salomé
authors.initials: S
authors.lastname: González-Reyes
authors.forename: José Manuel
authors.initials: JM
authors.lastname: del Casar
authors.forename: Francisco J
authors.initials: FJ
authors.lastname: Vizoso
mesh_terms: D051722:ADAM Proteins / Q000235:genetics / Q000378:metabolism; D017306:Annexin A2 / Q000235:genetics / Q000378:metabolism; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D002277:Carcinoma / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D054405:Chemokine CCL3 / Q000235:genetics / Q000378:metabolism; D062465:Claudin-3 / Q000235:genetics / Q000378:metabolism; D018450:Disease Progression; D005260:Female; D005500:Follow-Up Studies; D006801:Humans; D007249:Inflammation / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D016899:Interferon-beta / Q000235:genetics / Q000378:metabolism; D053592:Interleukin-1 Receptor-Associated Kinases / Q000235:genetics / Q000378:metabolism; D007378:Interleukins / Q000235:genetics / Q000378:metabolism; D007963:Leukocytes, Mononuclear / Q000378:metabolism / Q000473:pathology; D020781:Matrix Metalloproteinase 1 / Q000235:genetics / Q000378:metabolism; D053507:Matrix Metalloproteinase 11 / Q000235:genetics / Q000378:metabolism; D053594:Myeloid Differentiation Factor 88 / Q000235:genetics / Q000378:metabolism; D016328:NF-kappa B / Q000235:genetics / Q000378:metabolism; D009362:Neoplasm Metastasis; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D015854:Up-Regulation / Q000235:genetics
chemical_list: C472822:ANXA2 protein, human; D017306:Annexin A2; C515429:CCL3 protein, human; D054405:Chemokine CCL3; D062465:Claudin-3; D007378:Interleukins; C507779:MYD88 protein, human; D053594:Myeloid Differentiation Factor 88; D016328:NF-kappa B; C560822:TIMP1 protein, human; D019715:Tissue Inhibitor of Metalloproteinase-1; D016899:Interferon-beta; C507773:IRAK4 protein, human; D053592:Interleukin-1 Receptor-Associated Kinases; D051722:ADAM Proteins; D053507:Matrix Metalloproteinase 11; D020781:Matrix Metalloproteinase 1