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The matrix metalloproteinase 7 (MMP7) links Hsp90 chaperone with acquired drug resistance and tumor metastasis

BACKGROUND: Cancer emergence is associated with a series of cellular transformations that include acquired drug resistance followed by tumor metastasis. Matrix metalloproteinases (MMPs) and Hsp90 chaperone are implicated in tumor progression, however, they are not studied in the context of drug resi...

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Autores principales: Kumar, Pankaj, Siripini, Satish, Sreedhar, Amere Subbarao
Formato: Online Artículo Texto
Lenguaje:English
Publicado: John Wiley and Sons Inc. 2020
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9780424/
https://www.ncbi.nlm.nih.gov/pubmed/32761892
http://dx.doi.org/10.1002/cnr2.1261
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author Kumar, Pankaj
Siripini, Satish
Sreedhar, Amere Subbarao
author_facet Kumar, Pankaj
Siripini, Satish
Sreedhar, Amere Subbarao
author_sort Kumar, Pankaj
collection PubMed
description BACKGROUND: Cancer emergence is associated with a series of cellular transformations that include acquired drug resistance followed by tumor metastasis. Matrix metalloproteinases (MMPs) and Hsp90 chaperone are implicated in tumor progression, however, they are not studied in the context of drug resistance. AIMS: In the present study, we aimed at understanding the cross‐talk between acquired drug resistance and tumor progression, linking MMP7 and Hsp90. METHODS AND RESULTS: We have developed an in vitro model system for acquired drug resistance and studied the correlation between MMP7 and Hsp90. We demonstrate that enhanced drug efflux activity correlates with the induced expression and activity of MMP7, and enhanced metastatic potential of cells, however, in Hsp90‐dependent manner. The MMP7 overexpression alone could enhance the drug efflux activity marginally, and metastasis significantly. However, challenging these cells with 17AAG has significantly increased the drug efflux activity and, in contrast, decreased the metastatic potential. Evaluating our in vitro findings in mice xenografts revealed that MMP7 overexpression facilitates altered homing properties. However, these cells, in response to 17AAG treatment, exhibited increased localized tumor growth but decreased tumor metastasis. CONCLUSION: We demonstrated a cross‐talk between Hsp90 and MMP7 in regulating the acquired drug resistance and tumor progression. Our findings provide novel insights on targeting drug resistant‐tumors.
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spelling pubmed-97804242022-12-27 The matrix metalloproteinase 7 (MMP7) links Hsp90 chaperone with acquired drug resistance and tumor metastasis Kumar, Pankaj Siripini, Satish Sreedhar, Amere Subbarao Cancer Rep (Hoboken) Original Articles BACKGROUND: Cancer emergence is associated with a series of cellular transformations that include acquired drug resistance followed by tumor metastasis. Matrix metalloproteinases (MMPs) and Hsp90 chaperone are implicated in tumor progression, however, they are not studied in the context of drug resistance. AIMS: In the present study, we aimed at understanding the cross‐talk between acquired drug resistance and tumor progression, linking MMP7 and Hsp90. METHODS AND RESULTS: We have developed an in vitro model system for acquired drug resistance and studied the correlation between MMP7 and Hsp90. We demonstrate that enhanced drug efflux activity correlates with the induced expression and activity of MMP7, and enhanced metastatic potential of cells, however, in Hsp90‐dependent manner. The MMP7 overexpression alone could enhance the drug efflux activity marginally, and metastasis significantly. However, challenging these cells with 17AAG has significantly increased the drug efflux activity and, in contrast, decreased the metastatic potential. Evaluating our in vitro findings in mice xenografts revealed that MMP7 overexpression facilitates altered homing properties. However, these cells, in response to 17AAG treatment, exhibited increased localized tumor growth but decreased tumor metastasis. CONCLUSION: We demonstrated a cross‐talk between Hsp90 and MMP7 in regulating the acquired drug resistance and tumor progression. Our findings provide novel insights on targeting drug resistant‐tumors. John Wiley and Sons Inc. 2020-08-06 /pmc/articles/PMC9780424/ /pubmed/32761892 http://dx.doi.org/10.1002/cnr2.1261 Text en © 2020 The Authors. Cancer Reports published by Wiley Periodicals LLC. https://creativecommons.org/licenses/by/4.0/This is an open access article under the terms of the http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
spellingShingle Original Articles
Kumar, Pankaj
Siripini, Satish
Sreedhar, Amere Subbarao
The matrix metalloproteinase 7 (MMP7) links Hsp90 chaperone with acquired drug resistance and tumor metastasis
title The matrix metalloproteinase 7 (MMP7) links Hsp90 chaperone with acquired drug resistance and tumor metastasis
title_full The matrix metalloproteinase 7 (MMP7) links Hsp90 chaperone with acquired drug resistance and tumor metastasis
title_fullStr The matrix metalloproteinase 7 (MMP7) links Hsp90 chaperone with acquired drug resistance and tumor metastasis
title_full_unstemmed The matrix metalloproteinase 7 (MMP7) links Hsp90 chaperone with acquired drug resistance and tumor metastasis
title_short The matrix metalloproteinase 7 (MMP7) links Hsp90 chaperone with acquired drug resistance and tumor metastasis
title_sort matrix metalloproteinase 7 (mmp7) links hsp90 chaperone with acquired drug resistance and tumor metastasis
topic Original Articles
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC9780424/
https://www.ncbi.nlm.nih.gov/pubmed/32761892
http://dx.doi.org/10.1002/cnr2.1261
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