Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potentialReportar como inadecuado




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BMC Cancer

, 9:20

First Online: 14 January 2009Received: 02 September 2008Accepted: 14 January 2009DOI: 10.1186-1471-2407-9-20

Cite this article as: Figueira, R.C., Gomes, L.R., Neto, J.S. et al. BMC Cancer 2009 9: 20. doi:10.1186-1471-2407-9-20

Abstract

BackgroundThe 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.

MethodsWe 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.

ResultsThe 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.

ConclusionOur 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.

AbbreviationsCMconditioned medium

ECMextracellular matrix

ERestrogen receptor

MMPmatrix metalloproteinases

PRprogesterone receptor

qRT-PCRquantitative reverse transcription polymerase chain reaction

RECKreversion-inducing cysteine-rich protein with Kazal motifs

SDstandard deviation

TIMPtissue inhibitors of matrix metalloproteinases

Electronic supplementary materialThe online version of this article doi:10.1186-1471-2407-9-20 contains supplementary material, which is available to authorized users.

Rita CS Figueira, Luciana R Gomes contributed equally to this work.

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Autor: Rita CS Figueira - Luciana R Gomes - João S Neto - Fabricio C Silva - Ismael DCG Silva - Mari C Sogayar

Fuente: https://link.springer.com/







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