Immunosuppressive glycoproteins associate with breast tumor fibrosis and aggression

Matrix Biology Plus

Connor Stashko¹  Alastair J. Ironside²  E. Shelley Hwang³  Mary-Kate Hayward⁴  Valerie M. Weaver⁴  Kevin James Metcalf⁴  Eric Berens⁵ 

[1] Department of Bioengineering and Therapeutic Sciences, University of California, San Francisco, CA, United States;Department of Pathology, Western General Hospital, NHS Lothian, Edinburgh, United Kingdom;Department of Surgery, Duke University Medical Center, Durham, NC, United States;Department of Surgery, University of California, San Francisco, CA, United States;Knight Cancer Institute, Oregon Health and Science University, Portland, OR, United States;

关键词: Sialic acid;    Sialoglycoproteins;    Siglec receptors;    Breast cancer;    Fibrosis;   

DOI  :  

来源: DOAJ

【 摘 要 】

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.

【 授权许可】

Unknown