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

PLoS One. 2012;7(11):e49047. doi: 10.1371/journal.pone.0049047. Epub 2012 Nov 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ADAM Proteins / genetics
  • ADAM Proteins / metabolism
  • Annexin A2 / genetics
  • Annexin A2 / metabolism
  • Breast Neoplasms / genetics
  • Breast Neoplasms / metabolism*
  • Breast Neoplasms / pathology*
  • Carcinoma / genetics
  • Carcinoma / metabolism*
  • Carcinoma / pathology*
  • Chemokine CCL3 / genetics
  • Chemokine CCL3 / metabolism
  • Claudin-3 / genetics
  • Claudin-3 / metabolism
  • Disease Progression
  • Female
  • Follow-Up Studies
  • Humans
  • Inflammation / genetics
  • Inflammation / metabolism
  • Inflammation / pathology
  • Interferon-beta / genetics
  • Interferon-beta / metabolism
  • Interleukin-1 Receptor-Associated Kinases / genetics
  • Interleukin-1 Receptor-Associated Kinases / metabolism
  • Interleukins / genetics
  • Interleukins / metabolism
  • Leukocytes, Mononuclear / metabolism
  • Leukocytes, Mononuclear / pathology
  • Matrix Metalloproteinase 1 / genetics
  • Matrix Metalloproteinase 1 / metabolism
  • Matrix Metalloproteinase 11 / genetics
  • Matrix Metalloproteinase 11 / metabolism
  • Myeloid Differentiation Factor 88 / genetics
  • Myeloid Differentiation Factor 88 / metabolism
  • NF-kappa B / genetics
  • NF-kappa B / metabolism
  • Neoplasm Metastasis
  • Tissue Inhibitor of Metalloproteinase-1 / genetics
  • Tissue Inhibitor of Metalloproteinase-1 / metabolism
  • Up-Regulation / genetics

Substances

  • ANXA2 protein, human
  • Annexin A2
  • CCL3 protein, human
  • Chemokine CCL3
  • Claudin-3
  • Interleukins
  • MYD88 protein, human
  • Myeloid Differentiation Factor 88
  • NF-kappa B
  • TIMP1 protein, human
  • Tissue Inhibitor of Metalloproteinase-1
  • Interferon-beta
  • IRAK4 protein, human
  • Interleukin-1 Receptor-Associated Kinases
  • ADAM Proteins
  • Matrix Metalloproteinase 11
  • Matrix Metalloproteinase 1

Grants and funding

This work has been supported by grants from Fundación para la Investigación Científica y Tecnológica FICYT (EXPTE: IB08-170), Fondo de Inversión Sanitaria del Instituto de Salud Carlos III (FIS-PI10/02106) and FICEMU. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.