Serglycin as a potential biomarker for glioma: association of serglycin expression, extent of mast cell recruitment and glioblastoma progression
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Ananya Roy1,6, Sanaz Attarha1, Holger Weishaupt1, Per-Henrik Edqvist1,2, Fredrik J. Swartling1, Michael Bergqvist3, Florian A. Siebzehnrubl4, Anja Smits5,7, Fredrik Pontén1,2, Elena Tchougounova1
1Uppsala University, Department of Immunology, Genetics and Pathology, Rudbeck Laboratory, Uppsala, Sweden
2Science for Life Laboratory, Uppsala University, Uppsala, Sweden
3Umeå University, Department of Radiation Sciences, Umeå, Sweden
4Cardiff University School of Biosciences, European Cancer Stem Cell Research Institute, Cardiff, United Kingdom
5Uppsala University, Department of Neuroscience, Neurology, Uppsala, Sweden
6Swedish University of Agricultural Sciences, Department of Biomedical Sciences and Veterinary Public Health, Uppsala, Sweden
7Institute of Neuroscience and Physiology, Department of Clinical Neuroscience, Sahlgrenska Academy, Gothenburg University, Gothenburg, Sweden
Elena Tchougounova, email: [email protected]
Keywords: mast cell, glioma, serglycin, CD44, ZEB1
Received: January 12, 2017 Accepted: February 15, 2017 Published: March 01, 2017
Serglycin is an intracellular proteoglycan with a unique ability to adopt highly divergent structures by glycosylation with variable types of glycosaminoglycans (GAGs) when expressed by different cell types. Serglycin is overexpressed in aggressive cancers suggesting its protumorigenic role. In this study, we explored the expression of serglycin in human glioma and its correlation with survival and immune cell infiltration. We demonstrate that serglycin is expressed in glioma and that increased expression predicts poor survival of patients. Analysis of serglycin expression in a large cohort of low- and high-grade human glioma samples reveals that its expression is grade dependent and is positively correlated with mast cell (MC) infiltration. Moreover, serglycin expression in patient-derived glioma cells is significantly increased upon MC co-culture. This is also accompanied by increased expression of CXCL12, CXCL10, as well as markers of cancer progression, including CD44, ZEB1 and vimentin.
In conclusion, these findings indicate the importance of infiltrating MCs in glioma by modulating signaling cascades involving serglycin, CD44 and ZEB1. The present investigation reveals serglycin as a potential prognostic marker for glioma and demonstrates an association with the extent of MC recruitment and glioma progression, uncovering potential future therapeutic opportunities for patients.
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