Proteome and miRNome profiling of microvesicles derived from medulloblastoma cell lines with stem-like properties reveals biomarkers of poor prognosis

Author(s)

Kaid, Carolini ^[1] ; Assoni, Amanda ^[1] ; Marcola, Marina ^[1] ; Semedo-Kuriki, Patricia ^[1] ; Bortolin, Raul Hernandes ^[2] ; Carvalho, Valdemir Melechco ^[3] ; Okamoto, Oswaldo Keith ^{[1, 4]}

Affiliation

^[1] Univ Sao Paulo, Inst Biociencias, Ctr Pesquisa Genoma Humano & Celulas Tronco, Dept Genet Biol Evolut, Rua Matao 277, Cidade Univ, BR-05508090 Sao Paulo, SP - Brazil

^[2] Univ Sao Paulo, Sch Pharmaceut Sci, Dept Clin & Toxicol Anal, Sao Paulo - Brazil

^[3] Fleury Grp, Sao Paulo, SP - Brazil

^[4] Hosp Israelita Albert Einstein, Hemotherapy & Cellular Therapy Dept, Sao Paulo, SP - Brazil

• Document type: Review article
• Source: Brain Research; v. 1730, MAR 1 2020.
• Web of Science Citations: 0

Abstract

Primary central nervous system (CNS) tumors are the most common deadly childhood cancer. Several patients with medulloblastoma experience local or metastatic recurrences after standard treatment, a condition associated with very poor prognosis. Current neuroimaging techniques do not accurately detect residual stem-like medulloblastoma cells promoting tumor relapses. In attempt to identify candidate tumor markers that could be circulating in blood or cerebrospinal (CSF) fluid of patients, we evaluated the proteome and miRNome content of extracellular microvesicles (MVs) released by highly-aggressive stem-like medulloblastoma cells overexpressing the pluripotent factor OCT4A. These cells display enhanced tumor initiating capability and resistance to chemotherapeutic agents. A common set of 464 proteins and 10 microRNAs were exclusively detected in MVs of OCT4A-overexpressing cells from four distinct medulloblastoma cell lines, DAOY, CHLA-01-MED, D283-MED, and USP13-MED. The interactome mapping of these exclusive proteins and miRNAs revealed ERK, PI3K/AKT/mTOR, EGF/EGFR, and stem cell self-renewal as the main oncogenic signaling pathways altered in these aggressive medulloblastoma cells. Of these MV cargos, four proteins (UBE2M, HNRNPCL2, HNRNPCL3, HNRNPCL4) and five miRNAs (miR-4449, miR-500b, miR-3648, miR-1291, miR-3607) have not been previously reported in MVs from normal tissues and in CSF. These proteins and miRNAs carried within MVs might serve as biomarkers of aggressive stem-like medulloblastoma cells to improve clinical benefit by helping refining diagnosis, patient stratification, and early detection of relapsed disease. (AU)

• FAPESP's process: 13/08028-1 - CEGH-CEL - Human Genome and Stem Cell Research Center
• Grantee: Mayana Zatz
• Support Opportunities: Research Grants - Research, Innovation and Dissemination Centers - RIDC