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Increased matrix st...
Increased matrix stiffness enhances pro-tumorigenic traits in a physiologically relevant breast tissue- monocyte 3D model
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- Abrahamsson, Annelie (author)
- Linköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten
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- Rasti Boroojeni, Fatemeh (author)
- Linköpings universitet,Biofysik och bioteknik,Tekniska fakulteten,Laboratory of Molecular Materials
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- Naeimipour, Sajjad (author)
- Linköpings universitet,Biofysik och bioteknik,Tekniska fakulteten,Laboratory of Molecular Materials
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- Reustle, Nina (author)
- Linköpings universitet,Biofysik och bioteknik,Tekniska fakulteten,Laboratory of Molecular Materials
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- Selegård, Robert (author)
- Linköpings universitet,Biofysik och bioteknik,Tekniska fakulteten,Laboratory of Molecular Materials
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- Aili, Daniel (author)
- Linköpings universitet,Biofysik och bioteknik,Tekniska fakulteten,Laboratory of Molecular Materials
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- Dabrosin, Charlotta (author)
- Linköpings universitet,Avdelningen för kirurgi, ortopedi och onkologi,Medicinska fakulteten,Region Östergötland, Onkologiska kliniken US
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(creator_code:org_t)
- ELSEVIER SCI LTD, 2024
- 2024
- English.
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In: Acta Biomaterialia. - : ELSEVIER SCI LTD. - 1742-7061 .- 1878-7568. ; 178, s. 160-169
- Related links:
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
Subject headings
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- High mammographic density, associated with increased tissue stiffness, is a strong risk factor for breast cancer per se . In postmenopausal women there is no differences in the occurrence of ductal carcinoma in situ (DCIS) depending on breast density. Preliminary data suggest that dense breast tissue is associated with a pro -inflammatory microenvironment including infiltrating monocytes. However, the underlying mechanism(s) remains largely unknown. A major roadblock to understanding this risk factor is the lack of relevant in vitro models. A biologically relevant 3D model with tunable stiffness was developed by cross -linking hyaluronic acid. Breast cancer cells were cultured with and without freshly isolated human monocytes. In a unique clinical setting, extracellular proteins were sampled using microdialysis in situ from women with various breast densities. We show that tissue stiffness resembling high mammographic density increases the attachment of monocytes to the cancer cells, increase the expression of adhesion molecules and epithelia-mesenchymal-transition proteins in estrogen receptor (ER) positive breast cancer. Increased tissue stiffness results in increased secretion of similar pro-tumorigenic proteins as those found in human dense breast tissue including inflammatory cytokines, proteases, and growth factors. ER negative breast cancer cells were mostly unaffected suggesting that diverse cancer cell phenotypes may respond differently to tissue stiffness. We introduce a biological relevant model with tunable stiffness that resembles the densities found in normal breast tissue in women. The model will be key for further mechanistic studies. Additionally, our data revealed several pro-tumorigenic pathways that may be exploited for prevention and therapy against breast cancer.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinsk bioteknologi -- Medicinsk bioteknologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Medical Biotechnology -- Medical Biotechnology (hsv//eng)
Keyword
- Mammography; Microdialysis; Estrogen receptor
Publication and Content Type
- ref (subject category)
- art (subject category)
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