Human Breast Cancer Cell Lines Differentially Modulate Signaling from Distant Microenvironments, Which Reflects Their Metastatic Potential

Metastasis is the stage at which the prognosis substantially decreases for many types of cancer. The ability of tumor cells to metastasize is dependent upon the characteristics of the tumor cells, and the conditioning of distant tissues that support colonization by metastatic cells. In this report,...

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Main Authors: Ramon Ocadiz-Ruiz, Joseph T. Decker, Kate Griffin, Zoey M. Tan, Nishant K. Domala, Jacqueline S. Jeruss, Lonnie D. Shea
Format: Article
Language:English
Published: MDPI AG 2024-02-01
Series:Cancers
Subjects:
Online Access:https://www.mdpi.com/2072-6694/16/4/796
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author Ramon Ocadiz-Ruiz
Joseph T. Decker
Kate Griffin
Zoey M. Tan
Nishant K. Domala
Jacqueline S. Jeruss
Lonnie D. Shea
author_facet Ramon Ocadiz-Ruiz
Joseph T. Decker
Kate Griffin
Zoey M. Tan
Nishant K. Domala
Jacqueline S. Jeruss
Lonnie D. Shea
author_sort Ramon Ocadiz-Ruiz
collection DOAJ
description Metastasis is the stage at which the prognosis substantially decreases for many types of cancer. The ability of tumor cells to metastasize is dependent upon the characteristics of the tumor cells, and the conditioning of distant tissues that support colonization by metastatic cells. In this report, we investigated the systemic alterations in distant tissues caused by multiple human breast cancer cell lines and the impact of these alterations on the tumor cell phenotype. We observed that the niche within the lung, a common metastatic site, was significantly altered by MDA-MB-231, MCF7, and T47 tumors, and that the lung microenvironment stimulated, to differing extents, an epithelial-to-mesenchymal transition (EMT), reducing proliferation, increasing transendothelial migration and senescence, with no significant impact on cell death. We also investigated the ability of an implantable scaffold, which supports the formation of a distant tissue, to serve as a surrogate for the lung to identify systemic alterations. The scaffolds are conditioned by the primary tumor similarly to the lung for each tumor type, evidenced by promoting a pro-EMT profile. Collectively, we demonstrate that metastatic and non-metastatic breast cancers condition distant tissues, with distinct effects on tumor cell responses, and that a surrogate tissue can distinguish the metastatic potential of human breast cancer cell lines in an accessible site that avoids biopsy of a vital organ.
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spelling doaj.art-9e3e0f8eb7b14bcfbf2caa6f28cd05ce2024-02-23T15:11:15ZengMDPI AGCancers2072-66942024-02-0116479610.3390/cancers16040796Human Breast Cancer Cell Lines Differentially Modulate Signaling from Distant Microenvironments, Which Reflects Their Metastatic PotentialRamon Ocadiz-Ruiz0Joseph T. Decker1Kate Griffin2Zoey M. Tan3Nishant K. Domala4Jacqueline S. Jeruss5Lonnie D. Shea6Department of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USADepartment of Cariology, Restorative Sciences, and Endodontics, University of Michigan, Ann Arbor, MI 48109, USADepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USADepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USADepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USADepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USADepartment of Biomedical Engineering, University of Michigan, Ann Arbor, MI 48109, USAMetastasis is the stage at which the prognosis substantially decreases for many types of cancer. The ability of tumor cells to metastasize is dependent upon the characteristics of the tumor cells, and the conditioning of distant tissues that support colonization by metastatic cells. In this report, we investigated the systemic alterations in distant tissues caused by multiple human breast cancer cell lines and the impact of these alterations on the tumor cell phenotype. We observed that the niche within the lung, a common metastatic site, was significantly altered by MDA-MB-231, MCF7, and T47 tumors, and that the lung microenvironment stimulated, to differing extents, an epithelial-to-mesenchymal transition (EMT), reducing proliferation, increasing transendothelial migration and senescence, with no significant impact on cell death. We also investigated the ability of an implantable scaffold, which supports the formation of a distant tissue, to serve as a surrogate for the lung to identify systemic alterations. The scaffolds are conditioned by the primary tumor similarly to the lung for each tumor type, evidenced by promoting a pro-EMT profile. Collectively, we demonstrate that metastatic and non-metastatic breast cancers condition distant tissues, with distinct effects on tumor cell responses, and that a surrogate tissue can distinguish the metastatic potential of human breast cancer cell lines in an accessible site that avoids biopsy of a vital organ.https://www.mdpi.com/2072-6694/16/4/796metastasisbreast cancerscaffoldimplantmicroenvironmentEMT
spellingShingle Ramon Ocadiz-Ruiz
Joseph T. Decker
Kate Griffin
Zoey M. Tan
Nishant K. Domala
Jacqueline S. Jeruss
Lonnie D. Shea
Human Breast Cancer Cell Lines Differentially Modulate Signaling from Distant Microenvironments, Which Reflects Their Metastatic Potential
Cancers
metastasis
breast cancer
scaffold
implant
microenvironment
EMT
title Human Breast Cancer Cell Lines Differentially Modulate Signaling from Distant Microenvironments, Which Reflects Their Metastatic Potential
title_full Human Breast Cancer Cell Lines Differentially Modulate Signaling from Distant Microenvironments, Which Reflects Their Metastatic Potential
title_fullStr Human Breast Cancer Cell Lines Differentially Modulate Signaling from Distant Microenvironments, Which Reflects Their Metastatic Potential
title_full_unstemmed Human Breast Cancer Cell Lines Differentially Modulate Signaling from Distant Microenvironments, Which Reflects Their Metastatic Potential
title_short Human Breast Cancer Cell Lines Differentially Modulate Signaling from Distant Microenvironments, Which Reflects Their Metastatic Potential
title_sort human breast cancer cell lines differentially modulate signaling from distant microenvironments which reflects their metastatic potential
topic metastasis
breast cancer
scaffold
implant
microenvironment
EMT
url https://www.mdpi.com/2072-6694/16/4/796
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