3-D vascularized breast cancer model to study the role of osteoblast in formation of a pre-metastatic niche

Abstract Breast cancer cells (BCCs) preferentially metastasize to bone. It is known that BCCs remotely primes the distant bone site prior to metastasis. However, the reciprocal influence of bone cells on the primary tumor is relatively overlooked. Here, to study the bone-tumor paracrine influence, a...

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Autores principales:	Rahul Rimal, Prachi Desai, Andrea Bonnin Marquez, Karina Sieg, Yvonne Marquardt, Smriti Singh
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2021
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/891eee49a07947a5b73538b12c5dbd68
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spelling	oai:doaj.org-article:891eee49a07947a5b73538b12c5dbd682021-11-14T12:21:41Z3-D vascularized breast cancer model to study the role of osteoblast in formation of a pre-metastatic niche10.1038/s41598-021-01513-x2045-2322https://doaj.org/article/891eee49a07947a5b73538b12c5dbd682021-11-01T00:00:00Zhttps://doi.org/10.1038/s41598-021-01513-xhttps://doaj.org/toc/2045-2322Abstract Breast cancer cells (BCCs) preferentially metastasize to bone. It is known that BCCs remotely primes the distant bone site prior to metastasis. However, the reciprocal influence of bone cells on the primary tumor is relatively overlooked. Here, to study the bone-tumor paracrine influence, a tri-cellular 3-D vascularized breast cancer tissue (VBCTs) model is engineered which comprised MDA-MB231, a triple-negative breast cancer cells (TNBC), fibroblasts, and endothelial cells. This is indirectly co-cultured with osteoblasts (OBs), thereby constituting a complex quad-cellular tumor progression model. VBCTs alone and in conjunction with OBs led to abnormal vasculature and reduced vessel density but enhanced VEGF production. A total of 1476 significantly upregulated and 775 downregulated genes are identified in the VBCTs exposed to OBs. HSP90N, CYCS, RPS27A, and EGFR are recognized as upregulated hub-genes. Kaplan Meier plot shows HSP90N to have a significant outcome in TNBC patient survivability. Furthermore, compared to cancer tissues without vessels, gene analysis recognized 1278 significantly upregulated and 566 downregulated genes in VBCTs. DKK1, CXCL13, C3 protein and BMP4 are identified to be downregulated hub genes in VBCTs. Together, a multi-cellular breast cancer model and culture protocols are established to study pre-metastatic events in the presence of OBs.Rahul RimalPrachi DesaiAndrea Bonnin MarquezKarina SiegYvonne MarquardtSmriti SinghNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 11, Iss 1, Pp 1-16 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Rahul Rimal Prachi Desai Andrea Bonnin Marquez Karina Sieg Yvonne Marquardt Smriti Singh 3-D vascularized breast cancer model to study the role of osteoblast in formation of a pre-metastatic niche
description	Abstract Breast cancer cells (BCCs) preferentially metastasize to bone. It is known that BCCs remotely primes the distant bone site prior to metastasis. However, the reciprocal influence of bone cells on the primary tumor is relatively overlooked. Here, to study the bone-tumor paracrine influence, a tri-cellular 3-D vascularized breast cancer tissue (VBCTs) model is engineered which comprised MDA-MB231, a triple-negative breast cancer cells (TNBC), fibroblasts, and endothelial cells. This is indirectly co-cultured with osteoblasts (OBs), thereby constituting a complex quad-cellular tumor progression model. VBCTs alone and in conjunction with OBs led to abnormal vasculature and reduced vessel density but enhanced VEGF production. A total of 1476 significantly upregulated and 775 downregulated genes are identified in the VBCTs exposed to OBs. HSP90N, CYCS, RPS27A, and EGFR are recognized as upregulated hub-genes. Kaplan Meier plot shows HSP90N to have a significant outcome in TNBC patient survivability. Furthermore, compared to cancer tissues without vessels, gene analysis recognized 1278 significantly upregulated and 566 downregulated genes in VBCTs. DKK1, CXCL13, C3 protein and BMP4 are identified to be downregulated hub genes in VBCTs. Together, a multi-cellular breast cancer model and culture protocols are established to study pre-metastatic events in the presence of OBs.
format	article
author	Rahul Rimal Prachi Desai Andrea Bonnin Marquez Karina Sieg Yvonne Marquardt Smriti Singh
author_facet	Rahul Rimal Prachi Desai Andrea Bonnin Marquez Karina Sieg Yvonne Marquardt Smriti Singh
author_sort	Rahul Rimal
title	3-D vascularized breast cancer model to study the role of osteoblast in formation of a pre-metastatic niche
title_short	3-D vascularized breast cancer model to study the role of osteoblast in formation of a pre-metastatic niche
title_full	3-D vascularized breast cancer model to study the role of osteoblast in formation of a pre-metastatic niche
title_fullStr	3-D vascularized breast cancer model to study the role of osteoblast in formation of a pre-metastatic niche
title_full_unstemmed	3-D vascularized breast cancer model to study the role of osteoblast in formation of a pre-metastatic niche
title_sort	3-d vascularized breast cancer model to study the role of osteoblast in formation of a pre-metastatic niche
publisher	Nature Portfolio
publishDate	2021
url	https://doaj.org/article/891eee49a07947a5b73538b12c5dbd68
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3-D vascularized breast cancer model to study the role of osteoblast in formation of a pre-metastatic niche

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