Expression of metalloproteases and their inhibitors in different histological types of breast cancer.
ABSTRACT Metalloproteases (MMPs) and their tissue inhibitors of metalloproteases (TIMPs) are involved in several key aspects of tumoral growth, invasion and metastasis. The purpose of this study was to characterize on how the different histological types of breast cancer differ in the expression of several components of this enzymatic system.
An immunohistochemical study was performed in 50 ductal, 23 lobular, 14 mucinous, 7 tubular, 4 papillary and 5 medullary invasive carcinomas, using tissue arrays and specific antibodies against 7 MMPs and 3 tisullar TIMPs. Staining results were categorized by means of a specific software program (score values).
Carcinomas of the ductal type showed higher score values for MMPs and TIMPs than the other histological types; whereas mucinous carcinomas had lower scores values for expressions of the majority of these proteins. Stromal fibroblasts were more frequently positive for MMP-1, -7 and -13 and TIMP-1 and -3, when present in carcinomas of the ductal type than in other histological types of breast carcinomas. Stromal mononuclear inflammatory cells were more frequently positive for MMP-1 and TIMP-3, but more often negative for MMP-7, -9 and -11, when located in carcinomas of the ductal type than in other histological types of breast carcinomas.
We found variations in MMP/TIMP expressions among the different histological subtypes of breast carcinomas suggesting differences in their tumor pathophysiology.
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ABSTRACT: Matrix metalloproteinases (MMPs) are involved in cancer invasion and metastasis. Circulating tumor cells (CTCs) play role in tumor dissemination and are an independent survival predictor in breast cancer (BC) patients. The aim of this study was to assess correlation between CTCs and tumor MMP1 in BC.BMC Cancer 06/2014; 14(1):472. · 3.33 Impact Factor
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ABSTRACT: Cancer associated fibroblasts, CAFs, the most abundant cell type in breast cancer stroma, produce a plethora of chemokines, growth factors and ECM proteins, that may contribute to dissemination and metastasis. Axillary nodes are the first metastatic site in breast cancer, however, to the present date, there is no consensus of which specific proteins, synthesized by CAFs, might be related with lymph node involvement. The purpose of this study was to perform a systematic review of CAF biomarkers associated with the presence of regional metastasis. PubMed was searched using the words: "breast cancer" and "lymph node" and fibroblast or stroma or microenvironment. After exclusions, eight studies evaluating biomarkers immunoexpression in CAFs and lymph node status were selected. Biomarkers evaluated in these studies may be divided in two groups, according to their ontology: extracellular matrix components (MMP13, TIMP2, THBS1, LGALS1) and response to wounding (PDPN, PLAU, PLAUR, CAV1, THBS1, LGALS1). A positive expression of MMP13 and LGALS1 in CAFs was associated with enhanced odds ratio (OR) for regional metastasis. Contrariwise, CAV1 positive staining of fibroblasts was associated with decreased OR for nodal involvement. Expression of MMP13, PDPN and CAV1 was further tested in a new series of 65 samples of invasive ductal breast carcinomas by immunohistochemistry and no association between biomarkers expression in CAFs and nodal status was found. It was suggested that breast cancer subtypes may differentially affect CAFs behavior. It would be interesting to evaluate the prognostic significance of these biomarkers in CAFs from different tumor types.Bioscience Reports 11/2013; · 1.88 Impact Factor
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ABSTRACT: Background and aim: Matrix metalloproteinase-1 (MMP-1), a member of the MMP family of zinc-dependent endopeptidases, has been detected to be strongly expressed in gliomas with high tumor grade and to be correlated with increased tumor invasiveness. Vascular endothelial growth factor-C (VEGF-C), which is able to induce MMP-1 transcription, has been found to be upregulated in glioblastoma compared to low grade gliomas and non-neoplastic brain. The aim of the present study was to investigate the clinical significance of the co-expression of MMP-1 and VEGF-C in glioma patients on determining the prognosis. Methods: One hundred and sixteen glioma patients (26 World Health Organization (WHO) grade I, 30 WHO grade II, 30 WHO grade III, and 30 WHO grade IV) and 15 non-neoplastic brain specimens acquired from 15 patients undergoing surgery for epilepsy as control were collected. Immunohistochemistry was used to evaluate the expression of MMP-1 and VEGF-C in glioma and non-neoplastic brain tissues. The correlations of collaborative MMP-1 and VEGF-C expression with selected clinicopathologic parameters and clinical outcome of glioma patients were also assessed. Results: Both MMP-1 and VEGF-C expression were significantly higher in glioma tissues compared to non-neoplastic brain tissues (both P<0.001). Of 116 glioma patients, 68 (58.62%) overexpressed MMP-1 and VEGF-C simultaneously. In addition, combined MMP-1 and VEGF-C expression was significantly associated with WHO grade (P<0.001) and Karnofsky performance status (KPS) score (P=0.01). Moreover, glioma patients expressing both MMP-1 and VEGF-C exhibited markedly poorer overall survival (P<0.001). According to the multivariate analyses, collaborative overexpression of MMP-1 and VEGF-C was found to be an independent prognostic factor for overall survival (P=0.009). Conclusions: Our data demonstrated for the first time that overexpression of both MMP-1 and VEGF-C may be an independent poor prognostic factor in gliomas, suggesting the interaction between MMP-1 and VEGF-C collaboratively stimulated advanced tumor progression and adverse outcome. Inhibiting both MMP-1 and VEGF-C could be a novel therapeutic approach for gliomas.Cancer epidemiology. 07/2013;