From: The origins of breast cancer associated with mammographic density: a testable biological hypothesis
Tissue | Model | Biological effects | Two-stage model | References |
---|---|---|---|---|
Collagen | Transgenic mice (Col1a1) + PyVT transgene + MMTV promoter | 2.5-fold increase in stromal collagen + 3-fold increase tumor incidence | 1 + 2 | [38] |
Human MEC + collagen gel | Increase migration of cancer stem cells. | 2 | ||
Fibroblasts | Human MEC + stromal cells in mouse | Genetically modified human stromal fibroblasts promote outgrowth of benign and malignant lesions from MEC. | 1 + 2 | [41] |
Human cells in culture + mouse models | TGF-β and HGF produced by stromal fibroblasts inhibit and stimulate, respectively, proliferation in adjacent epithelial cells. | 1 + 2 | ||
TGF-β promotes epithelial-mesenchymal transition and changes in the microenvironment that promote tumor progression. | 2 | |||
Cancer associated fibroblasts (CAFs) | CAFs in stroma associated with breast cancer promote tumor dissemination. | 2 | ||
Other cells | Aromatase in stromal preadipocytes in various models including human breast tissue | Estrogen produced by aromatase increases MEC proliferation + tumor growth. | 1 + 2 | |
ECM | Human breast tissue | Â | Â | Â |
Proteoglycans | Overexpression of lumican and decorin in PMD and breast cancer bind growth factors. | 1 + 2 | [59] | |
MMP-3 | Metalloproteinases regulate stromal matrix and the activation of growth factors. | 1 + 2 | ||
Stiffness | Promotes tumorigenesis and growth | Â |