Table of Contents Author Guidelines Submit a Manuscript
BioMed Research International
Volume 2013, Article ID 279505, 15 pages
http://dx.doi.org/10.1155/2013/279505
Research Article

MMP1, MMP9, and COX2 Expressions in Promonocytes Are Induced by Breast Cancer Cells and Correlate with Collagen Degradation, Transformation-Like Morphological Changes in MCF-10A Acini, and Tumor Aggressiveness

1Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Avenida Cuauhtémoc 330, Colonia Doctores, Delegación Cuauhtémoc, 06720 México City, DF, Mexico
2Programa de Maestría en Ciencias Quimicobiológicas, Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional (IPN), Prolongación de Carpio y Plan de Ayala, Casco de Santo Tomás, 11340 México City, DF, Mexico
3Unidad de Investigación Médica en Enfermedades Oncológicas, Hospital de Oncología, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Avenida Cuauhtémoc 330, Colonia Doctores, Delegación Cuauhtémoc, 06720 México City, DF, Mexico
4Laboratorio de Inmunoalergia y Asma, Instituto Nacional de Enfermedades Respiratorias (INER), Calzada de Tlalpan 4502, Colonia Belisario Domínguez Sección, Delegación Tlalpan, 14080 México City, DF, Mexico
5Unidad de Investigación Médica en Inmunoquímica, Hospital de Especialidades, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social (IMSS), Avenida Cuauhtémoc 330, Colonia Doctores, Delegación Cuauhtémoc, 06720 México City, DF, Mexico
6Departamento de Morfología de la Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional (IPN), Prolongación de Carpio y Plan de Ayala, Casco de Santo Tomás, 11340 México City, DF, Mexico
7Departamento de Inmunología de la Escuela Nacional de Ciencias Biológicas, Instituto Politécnico Nacional (IPN), Prolongación de Carpio y Plan de Ayala, Casco de Santo Tomás, 11340 México City, DF, Mexico

Received 23 January 2013; Accepted 10 April 2013

Academic Editor: Mouldy Sioud

Copyright © 2013 G. K. Chimal-Ramírez et al. This is an open access article distributed under the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Tumor-associated immune cells often lack immune effector activities, and instead they present protumoral functions. To understand how tumors promote this immunological switch, invasive and noninvasive breast cancer cell (BRC) lines were cocultured with a promonocytic cell line in a Matrigel-based 3D system. We hypothesized that if communication exists between tumor and immune cells, coculturing would result in augmented expression of genes associated with tumor malignancy. Upregulation of proteases MMP1 and MMP9 and inflammatory COX2 genes was found likely in response to soluble factors. Interestingly, changes were more apparent in promonocytes and correlated with the aggressiveness of the BRC line. Increased gene expression was confirmed by collagen degradation assays and immunocytochemistry of prostaglandin 2, a product of COX2 activity. Untransformed MCF-10A cells were then used as a sensor of soluble factors with transformation-like capabilities, finding that acini formed in the presence of supernatants of the highly aggressive BRC/promonocyte cocultures often exhibited total loss of the normal architecture. These data support that tumor cells can modify immune cell gene expression and tumor aggressiveness may importantly reside in this capacity. Modeling interactions in the tumor stroma will allow the identification of genes useful as cancer prognostic markers and therapy targets.