title: MMP-7 and SGCE as distinctive molecular factors in sporadic colorectal cancers from the mutator phenotype pathway.
abstract: Colorectal cancers (CRCs) from the suppressor and the mutator carcinogenic pathways display distinctive pathological and clinical features that remain not completely understood. In this context, the aim of this work was to study the differential expression of metalloproteinases and adhesion molecules related to cancer invasiveness in both groups of tumours. We analyzed 84 tissue specimens, 42 primary sporadic CRCs obtained from patients who underwent radical surgery, and its corresponding control tissues. According to microsatellite instability, 31 cancers showed low or null microsatellite instability (MSI-L/MSS) and 11 tumours displayed high microsatellite instability (MSI-H). Expression assays were established using the Oligo GEArray(R) human extracellular matrix and adhesion molecules microarray containing 114 genes. Real-time quantitative PCR (RT-qPCR) confirmed expression data from arrays, using TaqMan probes. Results from oligoarray expression analyses indicated that ITGA3, ITGA9, ITGB4, ITGB7 and MMP15 had significantly higher expression levels in MSI-H tumours versus MSS/MSI-L cancers, whereas COL12A1, CSPG2, FN1, MMP-7 and SGCE were down-regulated in tumours with high microsatellite instability when compared to the stable group. After RT-qPCR validation, two of these genes, MMP-7 and SGCE, were confirmed to have statistical differences between the two groups of tumours studied. In both cases, MSI-H tumours displayed significant lower expression levels than MSI-L/MSS tumours. In conclusion, these two distinctive molecular markers could be related to a diminished invasion in colorectal tumours from the mutator pathway, this may contribute to the understanding of the better patient prognosis conferred by this type of tumours.
authors.affiliation: Departamento de Bioquímica y Biología Molecular, Universidad Complutense, 28040-Madrid, Spain.
authors.forename: Paloma
authors.initials: P
authors.lastname: Ortega
authors.forename: Alberto
authors.initials: A
authors.lastname: Moran
authors.forename: Tamara
authors.initials: T
authors.lastname: Fernandez-Marcelo
authors.forename: Carmen
authors.initials: C
authors.lastname: De Juan
authors.forename: Cristina
authors.initials: C
authors.lastname: Frias
authors.forename: José-Antonio
authors.initials: JA
authors.lastname: Lopez-Asenjo
authors.forename: Andrés
authors.initials: A
authors.lastname: Sanchez-Pernaute
authors.forename: Antonio
authors.initials: A
authors.lastname: Torres
authors.forename: Eduardo
authors.initials: E
authors.lastname: Diaz-Rubio
authors.forename: Pilar
authors.initials: P
authors.lastname: Iniesta
authors.forename: Manuel
authors.initials: M
authors.lastname: Benito
mesh_terms: D015815:Cell Adhesion Molecules / Q000378:metabolism; D045744:Cell Line, Tumor; D015179:Colorectal Neoplasms / Q000378:metabolism*; D005109:Extracellular Matrix / Q000378:metabolism; D020869:Gene Expression Profiling; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D020783:Matrix Metalloproteinase 7 / Q000378:metabolism*; D053842:Microsatellite Instability; D018895:Microsatellite Repeats / Q000235:genetics; D009154:Mutation; D009361:Neoplasm Invasiveness; D020411:Oligonucleotide Array Sequence Analysis; D049031:Sarcoglycans / Q000096:biosynthesis*
chemical_list: D015815:Cell Adhesion Molecules; C526572:SGCE protein, human; D049031:Sarcoglycans; D020783:Matrix Metalloproteinase 7