Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential
| Autor: | Luciana Rodrigues Gomes, João S Neto, Ismael Dale Cotrim Guerreiro da Silva, Mari Cleide Sogayar, Fabricio Colacino Silva, Rita C S Figueira |
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| Přispěvatelé: | Universidade de São Paulo (USP), Hosp Canc Alfredo Abrao, Universidade Federal de São Paulo (UNIFESP) |
| Rok vydání: | 2009 |
| Předmět: |
Cancer Research
Pathology medicine.medical_specialty Breast Neoplasms Biology Matrix metalloproteinase GPI-Linked Proteins lcsh:RC254-282 Breast cancer Surgical oncology Cell Line Tumor Matrix Metalloproteinase 14 Genetics medicine Humans Neoplasm Invasiveness RNA Messenger Neoplasm Metastasis Tissue Inhibitor of Metalloproteinase-2 Matrigel Membrane Glycoproteins Tissue Inhibitor of Metalloproteinase-1 Reverse Transcriptase Polymerase Chain Reaction Tissue Inhibitor of Metalloproteinases lcsh:Neoplasms. Tumors. Oncology. Including cancer and carcinogens medicine.disease Primary tumor Matrix Metalloproteinases Matrix Metalloproteinase 9 Oncology Cell culture Cancer research Matrix Metalloproteinase 2 Stem cell Signal transduction Research Article |
| Zdroj: | Repositório Institucional da UNIFESP Universidade Federal de São Paulo (UNIFESP) instacron:UNIFESP BMC Cancer, Vol 9, Iss 1, p 20 (2009) BMC Cancer |
| ISSN: | 1471-2407 |
| Popis: | Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP) Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq) Financiadora de Estudos e Projetos (FINEP) Pro-Reitoria da Universidade de São Paulo (PRP-USP) Background: the metastatic disease rather than the primary tumor itself is responsible for death in most solid tumors, including breast cancer. the role of matrix metalloproteinases ( MMPs), tissue inhibitors of MMPs (TIMPs) and Reversion-inducing cysteine-rich protein with Kazal motifs ( RECK) in the metastatic process has previously been established. However, in all published studies only a limited number of MMPs/MMP inhibitors was analyzed in a limited number of cell lines. Here, we propose a more comprehensive approach by analyzing the expression levels of several MMPs (MMP-2, MMP-9 and MMP-14) and MMP inhibitors (TIMP-1, TIMP-2 and RECK) in different models ( five human breast cancer cell lines, 72 primary breast tumors and 30 adjacent normal tissues).Methods: We analyzed the expression levels of MMP-2, MMP-9 and MMP-14 and their inhibitors (TIMP-1, TIMP-2 and RECK) by quantitative RT-PCR (qRT-PCR) in five human breast cancer cell lines presenting increased invasiveness and metastatic potential, 72 primary breast tumors and 30 adjacent normal tissues. Moreover, the role of cell-extracellular matrix elements interactions in the regulation of expression and activity of MMPs and their inhibitors was analyzed by culturing these cell lines on plastic or on artificial ECM (Matrigel).Results: the results demonstrated that MMPs mRNA expression levels displayed a positive and statistically significant correlation with the transcriptional expression levels of their inhibitors both in the cell line models and in the tumor tissue samples. Furthermore, the expression of all MMP inhibitors was modulated by cell-Matrigel contact only in highly invasive and metastatic cell lines. the enzyme/inhibitor balance at the transcriptional level significantly favors the enzyme which is more evident in tumor than in adjacent non-tumor tissue samples.Conclusion: Our results suggest that the expression of MMPs and their inhibitors, at least at the transcriptional level, might be regulated by common factors and signaling pathways. Therefore, the multi-factorial analysis of these molecules could provide new and independent prognostic information contributing to the determination of more adequate therapy strategies for each patient.` Univ São Paulo, Dept Biochem, Inst Chem, São Paulo, Brazil Hosp Canc Alfredo Abrao, Campo Grande, MS, Brazil Universidade Federal de São Paulo, Dept Gynecol, São Paulo, Brazil Universidade Federal de São Paulo, Dept Gynecol, São Paulo, Brazil Web of Science |
| Databáze: | OpenAIRE |
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