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A 3-D in vitro co-culture model of mammary gland involution
- Source :
- Integrative Biology
- Publication Year :
- 2014
- Publisher :
- Oxford University Press (OUP), 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.
- Subjects :
- STAT3 Transcription Factor
medicine.medical_specialty
Programmed cell death
Stromal cell
medicine.medical_treatment
Mammary gland
Biophysics
Oncostatin M
In Vitro Techniques
Biochemistry
Mice
Mammary Glands, Animal
Internal medicine
3T3-L1 Cells
medicine
Animals
Involution (medicine)
Mammary gland involution
Microscopy, Confocal
Cell Death
Tissue Engineering
Tissue Scaffolds
Chemistry
Regeneration (biology)
Macrophages
Epithelial Cells
Cell biology
medicine.anatomical_structure
Endocrinology
Cytokine
Cell culture
Female
Stromal Cells
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Integrative Biology
- Accession number :
- edsair.doi.dedup.....a2e365045d369a8861f0f8fbd9a9e3dc