Regulation of amyloid-β levels by matrix metalloproteinase-2/9 (MMP2/9) in the media of lung cancer cells

Abstract In this study, we set out to identify regulators of intact amyloid-β40/42 (Aβ) levels in A549 (p53 wild-type) and H1299 (p53-null) lung cancer cell media. Higher Aβ levels were detected in the media of A549 than H1299 cells without or with treatment with 4-methylumbelliferone (4-MU) and/or...

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Autores principales:	Sadaf Dorandish, Asana Williams, Sarah Atali, Sophia Sendo, Deanna Price, Colton Thompson, Jeffrey Guthrie, Deborah Heyl, Hedeel Guy Evans
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/d44d3e5714664754893ba718f40c07d2
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spelling	oai:doaj.org-article:d44d3e5714664754893ba718f40c07d22021-12-02T14:49:25ZRegulation of amyloid-β levels by matrix metalloproteinase-2/9 (MMP2/9) in the media of lung cancer cells10.1038/s41598-021-88574-02045-2322https://doaj.org/article/d44d3e5714664754893ba718f40c07d22021-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88574-0https://doaj.org/toc/2045-2322Abstract In this study, we set out to identify regulators of intact amyloid-β40/42 (Aβ) levels in A549 (p53 wild-type) and H1299 (p53-null) lung cancer cell media. Higher Aβ levels were detected in the media of A549 than H1299 cells without or with treatment with 4-methylumbelliferone (4-MU) and/or the anti-CD44 antibody (5F12). Using inhibitors, we found that PI3K, AKT, and NFκB are likely involved in regulating Aβ levels in the media. However, increased Aβ levels that more closely resembled those found upon 4-MU co-treatment resulted from MMP2/9 inhibition, suggesting that MMP2/9 maybe the main contributors to regulation of Aβ levels in the media. Differences in Aβ levels might be accounted for, in part, by p53 since blocking p53 function in A549 cells resulted in decreased Aβ levels, increased MMP2/9 levels, increased PI3K/AKT activities and the phospho/total NFκB ratio. Using siRNA targeted against MMP2 or MMP9, we found increased Aβ levels in the media, however, MMP2 knockdown led to Aβ levels closely mimicking those detected by co-treatment with 4-MU. Cell viability or apoptosis upon treatment with either MMP2 or MMP9 siRNA along with Aβ immunodepletion, showed that MMP2 is the predominant regulator of the cytotoxic effects induced by Aβ in lung cancer cells.Sadaf DorandishAsana WilliamsSarah AtaliSophia SendoDeanna PriceColton ThompsonJeffrey GuthrieDeborah HeylHedeel Guy EvansNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-22 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sadaf Dorandish Asana Williams Sarah Atali Sophia Sendo Deanna Price Colton Thompson Jeffrey Guthrie Deborah Heyl Hedeel Guy Evans Regulation of amyloid-β levels by matrix metalloproteinase-2/9 (MMP2/9) in the media of lung cancer cells
description	Abstract In this study, we set out to identify regulators of intact amyloid-β40/42 (Aβ) levels in A549 (p53 wild-type) and H1299 (p53-null) lung cancer cell media. Higher Aβ levels were detected in the media of A549 than H1299 cells without or with treatment with 4-methylumbelliferone (4-MU) and/or the anti-CD44 antibody (5F12). Using inhibitors, we found that PI3K, AKT, and NFκB are likely involved in regulating Aβ levels in the media. However, increased Aβ levels that more closely resembled those found upon 4-MU co-treatment resulted from MMP2/9 inhibition, suggesting that MMP2/9 maybe the main contributors to regulation of Aβ levels in the media. Differences in Aβ levels might be accounted for, in part, by p53 since blocking p53 function in A549 cells resulted in decreased Aβ levels, increased MMP2/9 levels, increased PI3K/AKT activities and the phospho/total NFκB ratio. Using siRNA targeted against MMP2 or MMP9, we found increased Aβ levels in the media, however, MMP2 knockdown led to Aβ levels closely mimicking those detected by co-treatment with 4-MU. Cell viability or apoptosis upon treatment with either MMP2 or MMP9 siRNA along with Aβ immunodepletion, showed that MMP2 is the predominant regulator of the cytotoxic effects induced by Aβ in lung cancer cells.
format	article
author	Sadaf Dorandish Asana Williams Sarah Atali Sophia Sendo Deanna Price Colton Thompson Jeffrey Guthrie Deborah Heyl Hedeel Guy Evans
author_facet	Sadaf Dorandish Asana Williams Sarah Atali Sophia Sendo Deanna Price Colton Thompson Jeffrey Guthrie Deborah Heyl Hedeel Guy Evans
author_sort	Sadaf Dorandish
title	Regulation of amyloid-β levels by matrix metalloproteinase-2/9 (MMP2/9) in the media of lung cancer cells
title_short	Regulation of amyloid-β levels by matrix metalloproteinase-2/9 (MMP2/9) in the media of lung cancer cells
title_full	Regulation of amyloid-β levels by matrix metalloproteinase-2/9 (MMP2/9) in the media of lung cancer cells
title_fullStr	Regulation of amyloid-β levels by matrix metalloproteinase-2/9 (MMP2/9) in the media of lung cancer cells
title_full_unstemmed	Regulation of amyloid-β levels by matrix metalloproteinase-2/9 (MMP2/9) in the media of lung cancer cells
title_sort	regulation of amyloid-β levels by matrix metalloproteinase-2/9 (mmp2/9) in the media of lung cancer cells
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/d44d3e5714664754893ba718f40c07d2
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Regulation of amyloid-β levels by matrix metalloproteinase-2/9 (MMP2/9) in the media of lung cancer cells

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