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Table 1 Selected biological properties of components of breast stroma

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

[39, 40]

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

[42,43,44]

TGF-β promotes epithelial-mesenchymal transition and changes in the microenvironment that promote tumor progression.

2

[44, 45]

Cancer associated fibroblasts (CAFs)

CAFs in stroma associated with breast cancer promote tumor dissemination.

2

[42, 46,47,48,49, 56]

Other cells

Aromatase in stromal preadipocytes in various models including human breast tissue

Estrogen produced by aromatase increases MEC proliferation + tumor growth.

1 + 2

[50,51,52,53,54,55]

ECM

Human breast tissue

   

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

[60, 61]

Stiffness

Promotes tumorigenesis and growth

 

[57, 58]

  1. Abbreviations: ECM Extracellular matrix, MEC Mammary epithelial cell, PyVT Polyomavirus middle T antigen, MMTV Mouse mammary tumor virus, TGF-β Transforming growth factor-β, HGF Hepatocyte growth factor, MMP-3 Matrix metalloproteinase 3, PMD: Percent mammographic density