Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential
Autor(a) principal: | |
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Data de Publicação: | 2009 |
Outros Autores: | , , , , |
Tipo de documento: | Artigo |
Idioma: | eng |
Título da fonte: | Repositório Institucional da UNIFESP |
Texto Completo: | http://repositorio.unifesp.br/handle/11600/31247 http://dx.doi.org/10.1186/1471-2407-9-20 |
Resumo: | 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.` |
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Figueira, Rita C. S.Gomes, Luciana R.Neto, Joao S.Silva, Fabricio C.Silva, Ismael Dale Cotrim Guerreiro da [UNIFESP]Sogayar, Mari C.Universidade de São Paulo (USP)Hosp Canc Alfredo AbraoUniversidade Federal de São Paulo (UNIFESP)2016-01-24T13:52:11Z2016-01-24T13:52:11Z2009-01-14Bmc Cancer. London: Biomed Central Ltd, v. 9, 11 p., 2009.1471-2407http://repositorio.unifesp.br/handle/11600/31247http://dx.doi.org/10.1186/1471-2407-9-20WOS000263002200004.pdf10.1186/1471-2407-9-20WOS:000263002200004Background: 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.`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)Univ São Paulo, Dept Biochem, Inst Chem, São Paulo, BrazilHosp Canc Alfredo Abrao, Campo Grande, MS, BrazilUniversidade Federal de São Paulo, Dept Gynecol, São Paulo, BrazilUniversidade Federal de São Paulo, Dept Gynecol, São Paulo, BrazilWeb of Science11engBiomed Central LtdBmc CancerCorrelation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potentialinfo:eu-repo/semantics/publishedVersioninfo:eu-repo/semantics/articleinfo:eu-repo/semantics/openAccessreponame:Repositório Institucional da UNIFESPinstname:Universidade Federal de São Paulo (UNIFESP)instacron:UNIFESPORIGINALWOS000263002200004.pdfapplication/pdf606172${dspace.ui.url}/bitstream/11600/31247/1/WOS000263002200004.pdf7cbb1fad9664addd9a18d848c0c8f6e1MD51open accessTEXTWOS000263002200004.pdf.txtWOS000263002200004.pdf.txtExtracted texttext/plain44840${dspace.ui.url}/bitstream/11600/31247/2/WOS000263002200004.pdf.txted3a9bd1b160dca068a50a22171aa8b7MD52open access11600/312472022-02-18 10:09:39.462open accessoai:repositorio.unifesp.br:11600/31247Repositório InstitucionalPUBhttp://www.repositorio.unifesp.br/oai/requestopendoar:34652023-05-25T12:07:18.763263Repositório Institucional da UNIFESP - Universidade Federal de São Paulo (UNIFESP)false |
dc.title.en.fl_str_mv |
Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential |
title |
Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential |
spellingShingle |
Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential Figueira, Rita C. S. |
title_short |
Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential |
title_full |
Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential |
title_fullStr |
Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential |
title_full_unstemmed |
Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential |
title_sort |
Correlation between MMPs and their inhibitors in breast cancer tumor tissue specimens and in cell lines with different metastatic potential |
author |
Figueira, Rita C. S. |
author_facet |
Figueira, Rita C. S. Gomes, Luciana R. Neto, Joao S. Silva, Fabricio C. Silva, Ismael Dale Cotrim Guerreiro da [UNIFESP] Sogayar, Mari C. |
author_role |
author |
author2 |
Gomes, Luciana R. Neto, Joao S. Silva, Fabricio C. Silva, Ismael Dale Cotrim Guerreiro da [UNIFESP] Sogayar, Mari C. |
author2_role |
author author author author author |
dc.contributor.institution.none.fl_str_mv |
Universidade de São Paulo (USP) Hosp Canc Alfredo Abrao Universidade Federal de São Paulo (UNIFESP) |
dc.contributor.author.fl_str_mv |
Figueira, Rita C. S. Gomes, Luciana R. Neto, Joao S. Silva, Fabricio C. Silva, Ismael Dale Cotrim Guerreiro da [UNIFESP] Sogayar, Mari C. |
description |
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.` |
publishDate |
2009 |
dc.date.issued.fl_str_mv |
2009-01-14 |
dc.date.accessioned.fl_str_mv |
2016-01-24T13:52:11Z |
dc.date.available.fl_str_mv |
2016-01-24T13:52:11Z |
dc.type.status.fl_str_mv |
info:eu-repo/semantics/publishedVersion |
dc.type.driver.fl_str_mv |
info:eu-repo/semantics/article |
format |
article |
status_str |
publishedVersion |
dc.identifier.citation.fl_str_mv |
Bmc Cancer. London: Biomed Central Ltd, v. 9, 11 p., 2009. |
dc.identifier.uri.fl_str_mv |
http://repositorio.unifesp.br/handle/11600/31247 http://dx.doi.org/10.1186/1471-2407-9-20 |
dc.identifier.issn.none.fl_str_mv |
1471-2407 |
dc.identifier.file.none.fl_str_mv |
WOS000263002200004.pdf |
dc.identifier.doi.none.fl_str_mv |
10.1186/1471-2407-9-20 |
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WOS:000263002200004 |
identifier_str_mv |
Bmc Cancer. London: Biomed Central Ltd, v. 9, 11 p., 2009. 1471-2407 WOS000263002200004.pdf 10.1186/1471-2407-9-20 WOS:000263002200004 |
url |
http://repositorio.unifesp.br/handle/11600/31247 http://dx.doi.org/10.1186/1471-2407-9-20 |
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Biomed Central Ltd |
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Biomed Central Ltd |
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