MMP-2 mediates mesenchymal stem cell tropism towards medulloblastoma tumors

Matrix metalloproteinases (MMPs) are a family of proteinases known to play a role in cell migration. In the present study, we evaluated the role of MMP-2 on tropism of human cord blood derived stem cells (hUCBSCs) in a human medulloblastoma tumor model. Consequences of MMP-2 inhibition on stem cell...

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Main Authors:	Bhoopathi, Praveen, Chetty, Chandramu, Gogineni, Venkateswara Rao, Gujrati, Meena, Dinh, Dzung H., Rao, Jasti S., Lakka, Sajani S.
Format:	Online
Language:	English
Published:	2011
Online Access:	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123681/

id	pubmed-3123681
recordtype	oai_dc
spelling	pubmed-31236812012-01-01 MMP-2 mediates mesenchymal stem cell tropism towards medulloblastoma tumors Bhoopathi, Praveen Chetty, Chandramu Gogineni, Venkateswara Rao Gujrati, Meena Dinh, Dzung H. Rao, Jasti S. Lakka, Sajani S. Article Matrix metalloproteinases (MMPs) are a family of proteinases known to play a role in cell migration. In the present study, we evaluated the role of MMP-2 on tropism of human cord blood derived stem cells (hUCBSCs) in a human medulloblastoma tumor model. Consequences of MMP-2 inhibition on stem cell tropism towards medulloblastoma were studied in terms of stem cell migration by using cell culture inserts, transwell chamber assay, western blotting for MMP-2 and migratory molecules, and immunohistochemistry. Conditioned medium from Daoy/D283 cells infected with adenoviral vector encoding MMP-2 siRNA (Ad-MMP-2 si) reduced stem cell migration as compared to conditioned medium from mock and scrambled vector (Ad-SV) infected cells. In addition, MMP-2 inhibition in the tumor cells decreased the expression of SDF1 in the tumor conditioned medium, which results in impaired SDF1/CXCR4 signaling leading to decreased stem cell tropism towards the tumor cells. We further show that MMP-2 inhibition in the tumor cells repressed stem cell tropism towards medulloblastoma tumors in vivo. In summary, we conclude that hUCBSCs can integrate into human medulloblastoma after local delivery and that MMP-2 expression by the tumor cells mediates this response through the SDF1/CXCR4 axis. 2011-03-03 2011-07 /pmc/articles/PMC3123681/ /pubmed/21368903 http://dx.doi.org/10.1038/gt.2011.14 Text en Users may view, print, copy, download and text and data- mine the content in such documents, for the purposes of academic research, subject always to the full Conditions of use: http://www.nature.com/authors/editorial_policies/license.html#terms
repository_type	Open Access Journal
institution_category	Foreign Institution
institution	US National Center for Biotechnology Information
building	NCBI PubMed
collection	Online Access
language	English
format	Online
author	Bhoopathi, Praveen Chetty, Chandramu Gogineni, Venkateswara Rao Gujrati, Meena Dinh, Dzung H. Rao, Jasti S. Lakka, Sajani S.
spellingShingle	Bhoopathi, Praveen Chetty, Chandramu Gogineni, Venkateswara Rao Gujrati, Meena Dinh, Dzung H. Rao, Jasti S. Lakka, Sajani S. MMP-2 mediates mesenchymal stem cell tropism towards medulloblastoma tumors
author_facet	Bhoopathi, Praveen Chetty, Chandramu Gogineni, Venkateswara Rao Gujrati, Meena Dinh, Dzung H. Rao, Jasti S. Lakka, Sajani S.
author_sort	Bhoopathi, Praveen
title	MMP-2 mediates mesenchymal stem cell tropism towards medulloblastoma tumors
title_short	MMP-2 mediates mesenchymal stem cell tropism towards medulloblastoma tumors
title_full	MMP-2 mediates mesenchymal stem cell tropism towards medulloblastoma tumors
title_fullStr	MMP-2 mediates mesenchymal stem cell tropism towards medulloblastoma tumors
title_full_unstemmed	MMP-2 mediates mesenchymal stem cell tropism towards medulloblastoma tumors
title_sort	mmp-2 mediates mesenchymal stem cell tropism towards medulloblastoma tumors
description	Matrix metalloproteinases (MMPs) are a family of proteinases known to play a role in cell migration. In the present study, we evaluated the role of MMP-2 on tropism of human cord blood derived stem cells (hUCBSCs) in a human medulloblastoma tumor model. Consequences of MMP-2 inhibition on stem cell tropism towards medulloblastoma were studied in terms of stem cell migration by using cell culture inserts, transwell chamber assay, western blotting for MMP-2 and migratory molecules, and immunohistochemistry. Conditioned medium from Daoy/D283 cells infected with adenoviral vector encoding MMP-2 siRNA (Ad-MMP-2 si) reduced stem cell migration as compared to conditioned medium from mock and scrambled vector (Ad-SV) infected cells. In addition, MMP-2 inhibition in the tumor cells decreased the expression of SDF1 in the tumor conditioned medium, which results in impaired SDF1/CXCR4 signaling leading to decreased stem cell tropism towards the tumor cells. We further show that MMP-2 inhibition in the tumor cells repressed stem cell tropism towards medulloblastoma tumors in vivo. In summary, we conclude that hUCBSCs can integrate into human medulloblastoma after local delivery and that MMP-2 expression by the tumor cells mediates this response through the SDF1/CXCR4 axis.
publishDate	2011
url	https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3123681/
_version_	1611462256861642752

MMP-2 mediates mesenchymal stem cell tropism towards medulloblastoma tumors

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