Immunosuppressive glycoproteins associate with breast tumor fibrosis and aggression.

Autor:	Metcalf KJ; Department of Surgery, University of California, San Francisco, CA, United States., Hayward MK; Department of Surgery, University of California, San Francisco, CA, United States., Berens E; Knight Cancer Institute, Oregon Health and Science University, Portland, OR, United States., Ironside AJ; Department of Pathology, Western General Hospital, NHS Lothian, Edinburgh, United Kingdom., Stashko C; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, United States., Hwang ES; Department of Surgery, Duke University Medical Center, Durham, NC, United States., Weaver VM; Department of Surgery, University of California, San Francisco, CA, United States.; Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, United States.; Helen Diller Family Comprehensive Cancer Center, University of California, San Francisco, CA, United States.; Center for Bioengineering and Tissue Regeneration, University of California, San Francisco, CA, United States.; Department of Radiation Oncology, University of California, San Francisco, CA, United States.; Eli and Edythe Broad Center of Regeneration Medicine and Stem Cell Research, University of California, San Francisco, CA, United States.
Jazyk:	angličtina
Zdroj:	Matrix biology plus [Matrix Biol Plus] 2022 Mar 09; Vol. 14, pp. 100105. Date of Electronic Publication: 2022 Mar 09 (Print Publication: 2022).
DOI:	10.1016/j.mbplus.2022.100105
Abstrakt:	Tumors feature elevated sialoglycoprotein content. Sialoglycoproteins promote tumor progression and are linked to immune suppression via the sialic acid-Siglec axis. Understanding factors that increase sialoglycoprotein biosynthesis in tumors could identify approaches to improve patient response to immunotherapy. We quantified higher levels of sialoglycoproteins in the fibrotic regions within human breast tumor tissues. Human breast tumor subtypes, which are more fibrotic, similarly featured increased sialoglycoprotein content. Further analysis revealed the breast cancer cells as the primary cell type synthesizing and secreting the tumor tissue sialoglycoproteins and confirmed that the more aggressive, fibrotic breast cancer subtypes expressed the highest levels of sialoglycoprotein biosynthetic genes. The more aggressive breast cancer subtypes also featured greater infiltration of immunosuppressive SIGLEC7 , SIGLEC9 , and SIGLEC10 -pos myeloid cells, indicating that triple-negative breast tumors had higher expression of both immunosuppressive Siglec receptors and their cognate ligands. The findings link sialoglycoprotein biosynthesis and secretion to tumor fibrosis and aggression in human breast tumors. The data suggest targeting of the sialic acid-Siglec axis may comprise an attractive therapeutic target particularly for the more aggressive HER2+ and triple-negative breast cancer subtypes. Competing Interests: The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. (© 2022 The Author(s).)
Databáze:	MEDLINE
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