Collagen Mineralization Decreases NK Cell-Mediated Cytotoxicity of Breast Cancer Cells via Increased Glycocalyx Thickness

© 2024 Wiley‐VCH GmbH.

Bibliographische Detailangaben
Veröffentlicht in:Advanced materials (Deerfield Beach, Fla.). - 1998. - 36(2024), 43 vom: 07. Okt., Seite e2311505
1. Verfasser: Park, Sangwoo (VerfasserIn)
Weitere Verfasser: Choi, Siyoung, Shimpi, Adrian A, Estroff, Lara A, Fischbach, Claudia, Paszek, Matthew J
Format: Online-Aufsatz
Sprache:English
Veröffentlicht: 2024
Zugriff auf das übergeordnete Werk:Advanced materials (Deerfield Beach, Fla.)
Schlagworte:Journal Article Immune evasion bone extracellular matrix breast cancer collagen mineralization glycocalyx Collagen 9007-34-5 Collagen Type I
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500 |a UpdateOf: bioRxiv. 2024 Jan 23:2024.01.20.576377. doi: 10.1101/2024.01.20.576377. - PMID 38328161 
500 |a Citation Status MEDLINE 
520 |a © 2024 Wiley‐VCH GmbH. 
520 |a Skeletal metastasis is common in patients with advanced breast cancer and often caused by immune evasion of disseminated tumor cells (DTCs). In the skeleton, tumor cells not only disseminate to the bone marrow but also to osteogenic niches in which they interact with newly mineralizing bone extracellular matrix (ECM). However, it remains unclear how mineralization of collagen type I, the primary component of bone ECM, regulates tumor-immune cell interactions. Here, a combination of synthetic bone matrix models with controlled mineral content, nanoscale optical imaging, and flow cytometry are utilized to evaluate how collagen type I mineralization affects the biochemical and biophysical properties of the tumor cell glycocalyx, a dense layer of glycosylated proteins and lipids decorating their cell surface. These results suggest that collagen mineralization upregulates mucin-type O-glycosylation and sialylation by tumor cells, which increases their glycocalyx thickness while enhancing resistance to attack by natural killer (NK) cells. These changes are functionally linked as treatment with a sialylation inhibitor decreased mineralization-dependent glycocalyx thickness and made tumor cells more susceptible to NK cell attack. Together, these results suggest that interference with glycocalyx sialylation may represent a therapeutic strategy to enhance cancer immunotherapies targeting bone-metastatic breast cancer 
650 4 |a Journal Article 
650 4 |a Immune evasion 
650 4 |a bone extracellular matrix 
650 4 |a breast cancer 
650 4 |a collagen mineralization 
650 4 |a glycocalyx 
650 7 |a Collagen  |2 NLM 
650 7 |a 9007-34-5  |2 NLM 
650 7 |a Collagen Type I  |2 NLM 
700 1 |a Choi, Siyoung  |e verfasserin  |4 aut 
700 1 |a Shimpi, Adrian A  |e verfasserin  |4 aut 
700 1 |a Estroff, Lara A  |e verfasserin  |4 aut 
700 1 |a Fischbach, Claudia  |e verfasserin  |4 aut 
700 1 |a Paszek, Matthew J  |e verfasserin  |4 aut 
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773 1 8 |g volume:36  |g year:2024  |g number:43  |g day:07  |g month:10  |g pages:e2311505 
856 4 0 |u http://dx.doi.org/10.1002/adma.202311505  |3 Volltext 
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