Inhibition of glypican-1 expression induces an activated fibroblast phenotype in a human bone marrow-derived stromal cell-line

Abstract Cancer-associated fibroblasts (CAFs) are the most abundant stromal cell type in the tumor microenvironment. CAFs orchestrate tumor-stromal interactions, and contribute to cancer cell growth, metastasis, extracellular matrix (ECM) remodeling, angiogenesis, immunomodulation, and chemoresistan...

Descripción completa

Guardado en:

Detalles Bibliográficos
Autores principales:	Sukhneeraj P. Kaur, Arti Verma, Hee. K. Lee, Lillie M. Barnett, Payaningal R. Somanath, Brian S. Cummings
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/fba5e2b57e3647b6aa0552f214d90649
Etiquetas:	Agregar Etiqueta Sin Etiquetas, Sea el primero en etiquetar este registro!

id	oai:doaj.org-article:fba5e2b57e3647b6aa0552f214d90649
record_format	dspace
spelling	oai:doaj.org-article:fba5e2b57e3647b6aa0552f214d906492021-12-02T17:20:11ZInhibition of glypican-1 expression induces an activated fibroblast phenotype in a human bone marrow-derived stromal cell-line10.1038/s41598-021-88519-72045-2322https://doaj.org/article/fba5e2b57e3647b6aa0552f214d906492021-04-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-88519-7https://doaj.org/toc/2045-2322Abstract Cancer-associated fibroblasts (CAFs) are the most abundant stromal cell type in the tumor microenvironment. CAFs orchestrate tumor-stromal interactions, and contribute to cancer cell growth, metastasis, extracellular matrix (ECM) remodeling, angiogenesis, immunomodulation, and chemoresistance. However, CAFs have not been successfully targeted for the treatment of cancer. The current study elucidates the significance of glypican-1 (GPC-1), a heparan sulfate proteoglycan, in regulating the activation of human bone marrow-derived stromal cells (BSCs) of fibroblast lineage (HS-5). GPC-1 inhibition changed HS-5 cellular and nuclear morphology, and increased cell migration and contractility. GPC-1 inhibition also increased pro-inflammatory signaling and CAF marker expression. GPC-1 induced an activated fibroblast phenotype when HS-5 cells were exposed to prostate cancer cell conditioned media (CCM). Further, treatment of human bone-derived prostate cancer cells (PC-3) with CCM from HS-5 cells exhibiting GPC-1 loss increased prostate cancer cell aggressiveness. Finally, GPC-1 was expressed in mouse tibia bone cells and present during bone loss induced by mouse prostate cancer cells in a murine prostate cancer bone model. These data demonstrate that GPC-1 partially regulates the intrinsic and extrinsic phenotype of human BSCs and transformation into activated fibroblasts, identify novel functions of GPC-1, and suggest that GPC-1 expression in BSCs exerts inhibitory paracrine effects on the prostate cancer cells. This supports the hypothesis that GPC-1 may be a novel pharmacological target for developing anti-CAF therapeutics to control cancer.Sukhneeraj P. KaurArti VermaHee. K. LeeLillie M. BarnettPayaningal R. SomanathBrian S. CummingsNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-14 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sukhneeraj P. Kaur Arti Verma Hee. K. Lee Lillie M. Barnett Payaningal R. Somanath Brian S. Cummings Inhibition of glypican-1 expression induces an activated fibroblast phenotype in a human bone marrow-derived stromal cell-line
description	Abstract Cancer-associated fibroblasts (CAFs) are the most abundant stromal cell type in the tumor microenvironment. CAFs orchestrate tumor-stromal interactions, and contribute to cancer cell growth, metastasis, extracellular matrix (ECM) remodeling, angiogenesis, immunomodulation, and chemoresistance. However, CAFs have not been successfully targeted for the treatment of cancer. The current study elucidates the significance of glypican-1 (GPC-1), a heparan sulfate proteoglycan, in regulating the activation of human bone marrow-derived stromal cells (BSCs) of fibroblast lineage (HS-5). GPC-1 inhibition changed HS-5 cellular and nuclear morphology, and increased cell migration and contractility. GPC-1 inhibition also increased pro-inflammatory signaling and CAF marker expression. GPC-1 induced an activated fibroblast phenotype when HS-5 cells were exposed to prostate cancer cell conditioned media (CCM). Further, treatment of human bone-derived prostate cancer cells (PC-3) with CCM from HS-5 cells exhibiting GPC-1 loss increased prostate cancer cell aggressiveness. Finally, GPC-1 was expressed in mouse tibia bone cells and present during bone loss induced by mouse prostate cancer cells in a murine prostate cancer bone model. These data demonstrate that GPC-1 partially regulates the intrinsic and extrinsic phenotype of human BSCs and transformation into activated fibroblasts, identify novel functions of GPC-1, and suggest that GPC-1 expression in BSCs exerts inhibitory paracrine effects on the prostate cancer cells. This supports the hypothesis that GPC-1 may be a novel pharmacological target for developing anti-CAF therapeutics to control cancer.
format	article
author	Sukhneeraj P. Kaur Arti Verma Hee. K. Lee Lillie M. Barnett Payaningal R. Somanath Brian S. Cummings
author_facet	Sukhneeraj P. Kaur Arti Verma Hee. K. Lee Lillie M. Barnett Payaningal R. Somanath Brian S. Cummings
author_sort	Sukhneeraj P. Kaur
title	Inhibition of glypican-1 expression induces an activated fibroblast phenotype in a human bone marrow-derived stromal cell-line
title_short	Inhibition of glypican-1 expression induces an activated fibroblast phenotype in a human bone marrow-derived stromal cell-line
title_full	Inhibition of glypican-1 expression induces an activated fibroblast phenotype in a human bone marrow-derived stromal cell-line
title_fullStr	Inhibition of glypican-1 expression induces an activated fibroblast phenotype in a human bone marrow-derived stromal cell-line
title_full_unstemmed	Inhibition of glypican-1 expression induces an activated fibroblast phenotype in a human bone marrow-derived stromal cell-line
title_sort	inhibition of glypican-1 expression induces an activated fibroblast phenotype in a human bone marrow-derived stromal cell-line
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/fba5e2b57e3647b6aa0552f214d90649
work_keys_str_mv	AT sukhneerajpkaur inhibitionofglypican1expressioninducesanactivatedfibroblastphenotypeinahumanbonemarrowderivedstromalcellline AT artiverma inhibitionofglypican1expressioninducesanactivatedfibroblastphenotypeinahumanbonemarrowderivedstromalcellline AT heeklee inhibitionofglypican1expressioninducesanactivatedfibroblastphenotypeinahumanbonemarrowderivedstromalcellline AT lilliembarnett inhibitionofglypican1expressioninducesanactivatedfibroblastphenotypeinahumanbonemarrowderivedstromalcellline AT payaningalrsomanath inhibitionofglypican1expressioninducesanactivatedfibroblastphenotypeinahumanbonemarrowderivedstromalcellline AT brianscummings inhibitionofglypican1expressioninducesanactivatedfibroblastphenotypeinahumanbonemarrowderivedstromalcellline
_version_	1718381061568724992

Inhibition of glypican-1 expression induces an activated fibroblast phenotype in a human bone marrow-derived stromal cell-line

Ejemplares similares