최시영 (Cornell University) | 한빛사논문 > 한빛사

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조회339

최시영Siyoung Choi

Cornell University

Adv. Mater., Jan 27 2024, | https://doi.org/10.1002/adma.202311505 Collagen Mineralization Decreases NK Cell-Mediated Cytotoxicity of Breast Cancer Cells via Increased Glycocalyx Thickness

^1,2*Sangwoo Park, ^3*Siyoung Choi, ³Adrian A. Shimpi, ^4,5Lara A. Estroff, ^3,5#Claudia Fischbach, and ^1,2,5#Matthew J. Paszek

¹Graduate Field of Biophysics, Cornell University, Ithaca, NY 14853, USA

²Robert Frederick Smith School of Chemical and Biomolecular Engineering, Cornell University, Ithaca, NY 14853, USA

³Nancy E. and Peter C. Meinig School of Biomedical Engineering, Cornell University, Ithaca, NY 14853, USA

⁴Department of Materials Science and Engineering, Cornell University, Ithaca, NY, 14853, USA

⁵Kavli Institute at Cornell for Nanoscale Science, Cornell University, Ithaca, NY, 14853, USA

^*co-first authors,

^#co-corresponding authors: Claudia Fischbach, Matthew J Paszek

Abstract

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.

논문정보

형식Research article
게재일2024년 01월 (BRIC 등록일 2024-02-16)
연구진국외 연구진
분야 생명과학 > 구조생물 및 생물물리학

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