Role of CEACAM1, ECM, and Mesenchymal Stem Cells in an Orthotopic Model of Human Breast Cancer

Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) is a morphogen in an in vitro model for lumen formation and plays a similar role in breast epithelial cells implanted in humanized mammary fat pads in NOD-SCID mice. Although extra cellular matrix alone is sufficient to stimulate l...

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Main Authors: Sridhar Samineni, Carlotta Glackin, John E. Shively
Format: Article
Language:English
Published: Wiley 2011-01-01
Series:International Journal of Breast Cancer
Online Access:http://dx.doi.org/10.4061/2011/381080
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author Sridhar Samineni
Carlotta Glackin
John E. Shively
author_facet Sridhar Samineni
Carlotta Glackin
John E. Shively
author_sort Sridhar Samineni
collection DOAJ
description Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) is a morphogen in an in vitro model for lumen formation and plays a similar role in breast epithelial cells implanted in humanized mammary fat pads in NOD-SCID mice. Although extra cellular matrix alone is sufficient to stimulate lumen formation in CEACAM1 transfected MCF-7 cells grown in 3D culture, there is an additional requirement for stromal or mesenchymal cells (MSCs) for these cells to form xenografts with glandular structures in an orthotopic site. We demonstrate that optimal in vitro conditions include both Matrigel and MSCs and that the inclusion of collagen I inhibits xenograft differentiation. Additionally, there is no need to remove the nascent murine mammary gland. The previously observed difference in gland development between the long and short cytoplasmic domain isoforms of CEACAM1 is no longer observed in pregnant NOD/SCID mice suggesting that stimulation of the mammary fat pad by pregnancy critically affects xenograft differentiation.
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spelling doaj-art-82f2a2760fb5488ca25b6f22c87c4c752025-02-03T05:53:44ZengWileyInternational Journal of Breast Cancer2090-31892011-01-01201110.4061/2011/381080381080Role of CEACAM1, ECM, and Mesenchymal Stem Cells in an Orthotopic Model of Human Breast CancerSridhar Samineni0Carlotta Glackin1John E. Shively2Irell & Manella City of Hope Graduate School of Biological Sciences, Duarte, CA 91010, USADepartment of Neurosciences, Beckman Research Institute of City of Hope, Duarte, CA 91010, USADepartment of Immunology, Beckman Research Institute of City of Hope, Duarte, CA 91010, USACarcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) is a morphogen in an in vitro model for lumen formation and plays a similar role in breast epithelial cells implanted in humanized mammary fat pads in NOD-SCID mice. Although extra cellular matrix alone is sufficient to stimulate lumen formation in CEACAM1 transfected MCF-7 cells grown in 3D culture, there is an additional requirement for stromal or mesenchymal cells (MSCs) for these cells to form xenografts with glandular structures in an orthotopic site. We demonstrate that optimal in vitro conditions include both Matrigel and MSCs and that the inclusion of collagen I inhibits xenograft differentiation. Additionally, there is no need to remove the nascent murine mammary gland. The previously observed difference in gland development between the long and short cytoplasmic domain isoforms of CEACAM1 is no longer observed in pregnant NOD/SCID mice suggesting that stimulation of the mammary fat pad by pregnancy critically affects xenograft differentiation.http://dx.doi.org/10.4061/2011/381080
spellingShingle Sridhar Samineni
Carlotta Glackin
John E. Shively
Role of CEACAM1, ECM, and Mesenchymal Stem Cells in an Orthotopic Model of Human Breast Cancer
International Journal of Breast Cancer
title Role of CEACAM1, ECM, and Mesenchymal Stem Cells in an Orthotopic Model of Human Breast Cancer
title_full Role of CEACAM1, ECM, and Mesenchymal Stem Cells in an Orthotopic Model of Human Breast Cancer
title_fullStr Role of CEACAM1, ECM, and Mesenchymal Stem Cells in an Orthotopic Model of Human Breast Cancer
title_full_unstemmed Role of CEACAM1, ECM, and Mesenchymal Stem Cells in an Orthotopic Model of Human Breast Cancer
title_short Role of CEACAM1, ECM, and Mesenchymal Stem Cells in an Orthotopic Model of Human Breast Cancer
title_sort role of ceacam1 ecm and mesenchymal stem cells in an orthotopic model of human breast cancer
url http://dx.doi.org/10.4061/2011/381080
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AT johneshively roleofceacam1ecmandmesenchymalstemcellsinanorthotopicmodelofhumanbreastcancer