Bone Marrow-Derived Mesenchymal Stem Cells Migrate toward Hormone-Insensitive Prostate Tumor Cells Expressing TGF-β via N-Cadherin

The prostate tumor microenvironment plays important roles in the metastasis and hormone-insensitive re-growth of tumor cells. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are recruited into prostate tumors to facilitate tumor microenvironment formation. However, the specific intrinsic molecu...

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Autores principales:	Jinok Noh, Jinyeong Yu, Wootak Kim, Aran Park, Ki-Sook Park
Formato:	article
Lenguaje:	EN
Publicado:	MDPI AG 2021
Materias:	bone marrow-derived mesenchymal stem cell prostate tumor tumor microenvironment N-cadherin TGF-β Biology (General) QH301-705.5
Acceso en línea:	https://doaj.org/article/527cb936873544bf8da9d9adb8d02c2f
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spelling	oai:doaj.org-article:527cb936873544bf8da9d9adb8d02c2f2021-11-25T16:49:08ZBone Marrow-Derived Mesenchymal Stem Cells Migrate toward Hormone-Insensitive Prostate Tumor Cells Expressing TGF-β via N-Cadherin10.3390/biomedicines91115722227-9059https://doaj.org/article/527cb936873544bf8da9d9adb8d02c2f2021-10-01T00:00:00Zhttps://www.mdpi.com/2227-9059/9/11/1572https://doaj.org/toc/2227-9059The prostate tumor microenvironment plays important roles in the metastasis and hormone-insensitive re-growth of tumor cells. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are recruited into prostate tumors to facilitate tumor microenvironment formation. However, the specific intrinsic molecules mediating BM-MSCs’ migration to prostate tumors are unknown. BM-MSCs’ migration toward a conditioned medium (CM) of hormone-insensitive (PC3 and DU145) or hormone-sensitive (LNCaP) prostate tumor cells was investigated using a three-dimensional cell migration assay and a transwell migration assay. PC3 and DU145 expressed transforming growth factor-β (TGF-β), but LNCaP did not. Regardless of TGF-β expression, BM-MSCs migrated toward the CM of PC3, DU145, or LNCaP. The CM of PC3 or DU145 expressing TGF-β increased the phosphorylation of Smad2/3 in BM-MSCs. Inactivation of TGF-β signaling in BM-MSCs using TGF-β type 1 receptor (TGFBR1) inhibitors, SB505124, or SB431542 did not allow BM-MSCs to migrate toward the CM. The CM of PC3 or DU145 enhanced N-cadherin expression on BM-MSCs, but the LNCaP CM did not. SB505124, SB431542, and TGFBR1 knockdown prevented an increase in N-cadherin expression. N-cadherin knockdown inhibited the collective migration of BM-MSCs toward the PC3 CM. We identified N-cadherin as a mediator of BM-MSCs’ migration toward hormone-insensitive prostate tumor cells expressing TGF-β and introduced a novel strategy for controlling and re-engineering the prostate tumor microenvironment.Jinok NohJinyeong YuWootak KimAran ParkKi-Sook ParkMDPI AGarticlebone marrow-derived mesenchymal stem cellprostate tumortumor microenvironmentN-cadherinTGF-βBiology (General)QH301-705.5ENBiomedicines, Vol 9, Iss 1572, p 1572 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	bone marrow-derived mesenchymal stem cell prostate tumor tumor microenvironment N-cadherin TGF-β Biology (General) QH301-705.5
spellingShingle	bone marrow-derived mesenchymal stem cell prostate tumor tumor microenvironment N-cadherin TGF-β Biology (General) QH301-705.5 Jinok Noh Jinyeong Yu Wootak Kim Aran Park Ki-Sook Park Bone Marrow-Derived Mesenchymal Stem Cells Migrate toward Hormone-Insensitive Prostate Tumor Cells Expressing TGF-β via N-Cadherin
description	The prostate tumor microenvironment plays important roles in the metastasis and hormone-insensitive re-growth of tumor cells. Bone marrow-derived mesenchymal stem cells (BM-MSCs) are recruited into prostate tumors to facilitate tumor microenvironment formation. However, the specific intrinsic molecules mediating BM-MSCs’ migration to prostate tumors are unknown. BM-MSCs’ migration toward a conditioned medium (CM) of hormone-insensitive (PC3 and DU145) or hormone-sensitive (LNCaP) prostate tumor cells was investigated using a three-dimensional cell migration assay and a transwell migration assay. PC3 and DU145 expressed transforming growth factor-β (TGF-β), but LNCaP did not. Regardless of TGF-β expression, BM-MSCs migrated toward the CM of PC3, DU145, or LNCaP. The CM of PC3 or DU145 expressing TGF-β increased the phosphorylation of Smad2/3 in BM-MSCs. Inactivation of TGF-β signaling in BM-MSCs using TGF-β type 1 receptor (TGFBR1) inhibitors, SB505124, or SB431542 did not allow BM-MSCs to migrate toward the CM. The CM of PC3 or DU145 enhanced N-cadherin expression on BM-MSCs, but the LNCaP CM did not. SB505124, SB431542, and TGFBR1 knockdown prevented an increase in N-cadherin expression. N-cadherin knockdown inhibited the collective migration of BM-MSCs toward the PC3 CM. We identified N-cadherin as a mediator of BM-MSCs’ migration toward hormone-insensitive prostate tumor cells expressing TGF-β and introduced a novel strategy for controlling and re-engineering the prostate tumor microenvironment.
format	article
author	Jinok Noh Jinyeong Yu Wootak Kim Aran Park Ki-Sook Park
author_facet	Jinok Noh Jinyeong Yu Wootak Kim Aran Park Ki-Sook Park
author_sort	Jinok Noh
title	Bone Marrow-Derived Mesenchymal Stem Cells Migrate toward Hormone-Insensitive Prostate Tumor Cells Expressing TGF-β via N-Cadherin
title_short	Bone Marrow-Derived Mesenchymal Stem Cells Migrate toward Hormone-Insensitive Prostate Tumor Cells Expressing TGF-β via N-Cadherin
title_full	Bone Marrow-Derived Mesenchymal Stem Cells Migrate toward Hormone-Insensitive Prostate Tumor Cells Expressing TGF-β via N-Cadherin
title_fullStr	Bone Marrow-Derived Mesenchymal Stem Cells Migrate toward Hormone-Insensitive Prostate Tumor Cells Expressing TGF-β via N-Cadherin
title_full_unstemmed	Bone Marrow-Derived Mesenchymal Stem Cells Migrate toward Hormone-Insensitive Prostate Tumor Cells Expressing TGF-β via N-Cadherin
title_sort	bone marrow-derived mesenchymal stem cells migrate toward hormone-insensitive prostate tumor cells expressing tgf-β via n-cadherin
publisher	MDPI AG
publishDate	2021
url	https://doaj.org/article/527cb936873544bf8da9d9adb8d02c2f
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Bone Marrow-Derived Mesenchymal Stem Cells Migrate toward Hormone-Insensitive Prostate Tumor Cells Expressing TGF-β via N-Cadherin

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