Relationship between the inflammatory molecular profile of breast carcinomas and distant metastasis development

• Published in: PloS one 2012-11, Vol.7 (11), p.e49047-e49047
• Main Authors: Eiró, Noemí, González, Lucía, González, Luis O, Fernandez-Garcia, Belen, Lamelas, Maria Luz, Marín, Laura, González-Reyes, Salomé, del Casar, José Manuel, Vizoso, Francisco J
• Format: Article
• Language: English
• Subjects: ADAM Proteins - genetics; ADAM Proteins - metabolism; ADAMTS-1 protein; Analysis; Angiogenesis; Annexin A2 - genetics; Annexin A2 - metabolism; Annexins; B cells; Biology; Breast cancer; Breast carcinoma; Breast Neoplasms - genetics; Breast Neoplasms - metabolism; Breast Neoplasms - pathology; Carcinoma - genetics; Carcinoma - metabolism; Carcinoma - pathology; Chemokine CCL3 - genetics; Chemokine CCL3 - metabolism; Chemokines; Claudin-3 - genetics; Claudin-3 - metabolism; Cytokines; Disease Progression; Ethics; Female; Follow-Up Studies; Gene expression; Gene regulation; Growth factors; Humans; Inflammation; Inflammation - genetics; Inflammation - metabolism; Inflammation - pathology; Interferon-beta - genetics; Interferon-beta - metabolism; Interleukin 1; Interleukin 17; Interleukin 5; Interleukin 6; Interleukin-1 Receptor-Associated Kinases - genetics; Interleukin-1 Receptor-Associated Kinases - metabolism; Interleukins - genetics; Interleukins - metabolism; Interstitial collagenase; IRAK protein; Leukocytes, Mononuclear - metabolism; Leukocytes, Mononuclear - pathology; Matrix metalloproteinase; Matrix Metalloproteinase 1 - genetics; Matrix Metalloproteinase 1 - metabolism; Matrix Metalloproteinase 11 - genetics; Matrix Metalloproteinase 11 - metabolism; Medical prognosis; Medicine; Metalloproteinase; Metastases; Metastasis; MyD88 protein; Myeloid Differentiation Factor 88 - genetics; Myeloid Differentiation Factor 88 - metabolism; Neoplasm Metastasis; NF-kappa B - genetics; NF-kappa B - metabolism; NF-κB protein; Prognosis; Proteins; Tissue inhibitor of metalloproteinase 1; Tissue Inhibitor of Metalloproteinase-1 - genetics; Tissue Inhibitor of Metalloproteinase-1 - metabolism; Tumors; Up-Regulation - genetics; Womens health
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0049047

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.