title: 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.
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.
authors.affiliation: Unidad de Investigación Médica en Enfermedades Infecciosas y Parasitarias, Hospital de Pediatría, Centro Médico Nacional Siglo XXI, Instituto Mexicano del Seguro Social, Avenida Cuauhtémoc 330, Colonia Doctores, Delegación Cuauhtémoc, 06720 México City, DF, Mexico.
authors.forename: G K
authors.initials: GK
authors.lastname: Chimal-Ramírez
authors.forename: N A
authors.initials: NA
authors.lastname: Espinoza-Sánchez
authors.forename: D
authors.initials: D
authors.lastname: Utrera-Barillas
authors.forename: L
authors.initials: L
authors.lastname: Benítez-Bribiesca
authors.forename: J R
authors.initials: JR
authors.lastname: Velázquez
authors.forename: L A
authors.initials: LA
authors.lastname: Arriaga-Pizano
authors.forename: A
authors.initials: A
authors.lastname: Monroy-García
authors.forename: E
authors.initials: E
authors.lastname: Reyes-Maldonado
authors.forename: M L
authors.initials: ML
authors.lastname: Domínguez-López
authors.forename: Patricia
authors.initials: P
authors.lastname: Piña-Sánchez
authors.forename: E M
authors.initials: EM
authors.lastname: Fuentes-Pananá
mesh_terms: D061354:Acinar Cells / Q000378:metabolism / Q000473:pathology*; D001943:Breast Neoplasms / Q000235:genetics / Q000473:pathology*; D002450:Cell Communication / Q000235:genetics; D045744:Cell Line, Tumor; D002471:Cell Transformation, Neoplastic / Q000235:genetics / Q000473:pathology; D018920:Coculture Techniques; D003094:Collagen / Q000378:metabolism*; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism; D004847:Epithelial Cells / Q000378:metabolism / Q000473:pathology; D005109:Extracellular Matrix / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism*; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008954:Models, Biological; D055017:Monocyte-Macrophage Precursor Cells / Q000201:enzymology* / Q000473:pathology; D009361:Neoplasm Invasiveness; D010641:Phenotype; D059748:Proteolysis; D012995:Solubility; D015854:Up-Regulation
chemical_list: D003094:Collagen; D051546:Cyclooxygenase 2; C496540:PTGS2 protein, human; C579270:MMP9 protein, human; D020780:Matrix Metalloproteinase 9; C522360:MMP1 protein, human; D020781:Matrix Metalloproteinase 1; D015232:Dinoprostone