SRPX Emerges as a Potential Tumor Marker in the Extracellular Vesicles of Glioblastoma
by
,
Elisabet Ampudia-Mesias
1, 
Samia El-Hadad
2,
Charles Scott Cameron
1,
Adelheid Wöhrer
3,
Thomas Ströbel
3,
Nurten Saydam
4,† and
Okay Saydam
1,* 1
Department of Pediatrics, Division of Hematology and Oncology, Medical School, University of Minnesota, Minneapolis, MN 55454, USA
2
Department of Reproductive Endocrinology, University Hospital Zurich, 8006 Zurich, Switzerland
3
Division of Neuropathology and Neurochemistry, Department of Neurology, Medical University of Vienna, A-1090 Vienna, Austria
4
Department of Biochemistry, Molecular Biology, and Biophysics, Medical School, University of Minnesota, Minneapolis, MN 55454, USA
*
Author to whom correspondence should be addressed.
†
Previous address.
Cancers 2022, 14(8), 1984; https://doi.org/10.3390/cancers14081984
Submission received: 29 January 2022
/
Revised: 8 April 2022
/
Accepted: 10 April 2022
/
Published: 14 April 2022
(This article belongs to the Special Issue Bio-Pathological Markers for the Diagnosis and Therapy of Cancers, Volume II)
Simple Summary
Glioblastoma is the most common malignant primary brain tumor and remains incurable. Additionally, there are only a few non-invasive early diagnostic and prognostic markers for this disease. The stability of extracellular vesicles (EVs) and their availability in patient serum make them ideal for discovery of early markers associated with diagnosis, prognosis, and treatment response for glioblastoma. In this study, we used proteomics analysis to discover a novel tumor biomarker in glioblastoma human primary cell-derived EVs and found that sushi-repeat containing protein X-linked (SRPX) was the only protein identified in the majority of glioblastoma EVs that was absent in the HPA-derived EVs. Moreover, we further analyzed the possible role of SRPX in glioblastoma tumorigenesis and found that SRPX is involved in glioblastoma cell growth, and SRPX depletion sensitizes glioblastoma to temozolomide (TMZ). Taken together, our results suggest that SRPX can be used as a novel tumor biomarker for diagnostic and prognostic purposes for glioblastomas.
Abstract
Extracellular vesicles (EVs) may be used as a non-invasive screening platform to discover markers associated with early diagnosis, prognosis, and treatment response. Such an approach is invaluable for diseases such as glioblastoma, for which only a few non-invasive diagnostic or prognostic markers are available. We used mass spectrometry to analyze proteomics profiles of EVs derived from four glioblastoma cell lines and human primary astrocytes (HPAs) and found that SRPX is the only protein enriched in the majority of glioblastoma EVs that was absent in the HPA-derived EVs. Then, we evaluated the relationship between SRPX protein expression and tumor grade using immunohistochemical staining (IHC) and performed colony formation and viability assays to analyze the possible function of SRPX in glioblastoma. SRPX mRNA and protein expression were associated with tumor grade. Moreover, temozolomide (TMZ)-resistant tumor tissues showed highly positive SRPX staining, compared to all other tumor grades. Additionally, glioblastoma cells displayed enhanced SRPX gene expression when exposed to TMZ. Knockdown of SRPX gene expression via siRNA inhibited cell viability. Taken together, the results of this study suggest that SRPX can be used as a novel tumor marker for diagnostic and prognostic purposes and can also be a therapeutic target for glioblastomas.
Keywords:
SRPX; EVs; proteomics; glioblastoma
