NDLI: A 3-D <i>in vitro</i> co-culture model of mammary gland involution

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A 3-D in vitro co-culture model of mammary gland involution

Content Provider	Royal Society of Chemistry (RSC)
Author	Botos, Laur-Alexandru Watson, Christine J. Cameron, Ruth E. Campbell, Jonathan J. Davidenko, Natalia Sargeant, Timothy J.
Copyright Year	2014
Abstract	Involution is a process whereby the mammary gland undergoes extensive tissue remodelling involving exquisitely coordinated cell death, extracellular matrix degradation and adipose tissue regeneration following the weaning of offspring. These processes are mediated in part through Jak/Stat signalling pathways, which can be deregulated in breast cancer. Synthetic in vitro analogues of the breast could become important tools for studying tumorigenic processes, or as personalized drug discovery platforms and predictors of therapeutic response. Ideally, such models should support 3D neo-tissue formation, so as to recapitulate physiological organ function, and be compatible with high-throughput screening methodologies. We have combined cell lines of epithelial, stromal and immunological origin within engineered porous collagen/hyaluronic acid matrices, demonstrating 3D-specific molecular signatures. Furthermore seeded cells form mammary-like branched tissues, with lobuloalveolar structures that undergo inducible involution phenotypes reminiscent of the native gland under hormonal/cytokine regulation. We confirm that autophagy is mediated within differentiated mammary epithelial cells in a Stat-dependent manner at early time points following the removal of a prolactin stimulus (H/WD). In addition, epithelial cells express markers of an M2 macrophage lineage under H/WD, a process that is attenuated with the introduction of the monocyte/macrophage cell line RAW 264.7. Thus, such 3D models are suitable platforms for studying cell–cell interactions and cell death mechanisms in relation to cancer.
Starting Page	618
Ending Page	626
Page Count	9
File Format	HTM / HTML PDF
ISSN	17579694
Volume Number	6
Issue Number	6
Journal	Integrative Biology
DOI	10.1039/c3ib40257f
Language	English
Publisher	Royal Society of Chemistry
Access Restriction	Open
Subject Keyword	Involution (mathematics) Mammary gland Extracellular matrix Adipose tissue Janus kinase Breast cancer Drug discovery Three-dimensional space High-throughput screening Collagen Acid Semigroup with involution Cytokine Autophagy Prolactin Macrophage Monocyte Raw image format Cancer
Content Type	Text
Resource Type	Article
Subject	Medicine Biochemistry Biophysics

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4	Project PI / Joint PI	Principal Investigator and Joint Principal Investigators of the project	Dr. B. Sutradhar bsutra@ndl.gov.in Prof. Saswat Chakrabarti will be added soon
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J Mammary Gland Biol Neoplasia (2009) 14:145–157 DOI 10.1007/s10911-009-9118-8 Macrophages in Breast Cancer: Do Involution Macrophages Account for the Poor Prognosis of Pregnancy-Associated Breast Cancer? (2009)

MUC1 induces M2 type macrophage influx during postpartum mammary gland involution and triggers breast cancer

Stiff Collagen Matrices Increase Tumorigenic Prolactin Signaling in Breast Cancer Cells

3D microchannel co-culture: method and biological validation

J Mammary Gland Biol Neoplasia (2009) 14:181–191 DOI 10.1007/s10911-009-9123-y Mammary Involution and Breast Cancer Risk: Transgenic Models and Clinical Studies (2009)

The Multifaceted Role of STAT3 in Mammary Gland Involution and Breast Cancer

Mammary Gland Cell Death Also Involves Lysosomal Autophagy

Gene transcriptional networks integrate microenvironmental signals in human breast cancer

Induction of multidrug resistance transporter ABCG2 by prolactin in human breast cancer cells.

A 3-D in vitro co-culture model of mammary gland involution

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J Mammary Gland Biol Neoplasia (2009) 14:145–157 DOI 10.1007/s10911-009-9118-8 Macrophages in Breast Cancer: Do Involution Macrophages Account for the Poor Prognosis of Pregnancy-Associated Breast Cancer? (2009)

MUC1 induces M2 type macrophage influx during postpartum mammary gland involution and triggers breast cancer

Stiff Collagen Matrices Increase Tumorigenic Prolactin Signaling in Breast Cancer Cells

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J Mammary Gland Biol Neoplasia (2009) 14:181–191 DOI 10.1007/s10911-009-9123-y Mammary Involution and Breast Cancer Risk: Transgenic Models and Clinical Studies (2009)

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A 3-D in vitro co-culture model of mammary gland involution