Mechanical Pressure Driving Proteoglycan Expression in Mammographic Density: a Self-perpetuating Cycle?

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Reye, Gina
Huang, Xuan
Haupt, Larisa M
Murphy, Ryan J
Northey, Jason J
Thompson, Erik W
Momot, Konstantin I
Hugo, Honor J
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Regions of high mammographic density (MD) in the breast are characterised by a proteoglycan (PG)-rich fibrous stroma, where PGs mediate aligned collagen fibrils to control tissue stiffness and hence the response to mechanical forces. Literature is accumulating to support the notion that mechanical stiffness may drive PG synthesis in the breast contributing to MD. We review emerging patterns in MD and other biological settings, of a positive feedback cycle of force promoting PG synthesis, such as in articular cartilage, due to increased pressure on weight bearing joints. Furthermore, we present evidence to suggest a pro-tumorigenic effect of increased mechanical force on epithelial cells in contexts where PG-mediated, aligned collagen fibrous tissue abounds, with implications for breast cancer development attributable to high MD. Finally, we summarise means through which this positive feedback mechanism of PG synthesis may be intercepted to reduce mechanical force within tissues and thus reduce disease burden.

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Journal of Mammary Gland Biology and Neoplasia

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© The Author(s) 2021. This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made.

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Reye, G; Huang, X; Haupt, LM; Murphy, RJ; Northey, JJ; Thompson, EW; Momot, KI; Hugo, HJ, Mechanical Pressure Driving Proteoglycan Expression in Mammographic Density: a Self-perpetuating Cycle?, Journal of Mammary Gland Biology and Neoplasia, 2021