Metastatic Model of Cerebellar Medulloblastoma Cells to Peritoneal Cavity: Exploration of Circulating Tumor Cells
Keywords:Circulating tumor cells (CTCs), cerebellar medulloblastoma, peritoneal cavity, protein expression, Somatic/genomic heterogeneity, Metastatic model (MM).
Background: Circulating Tumor Cells (CTCs) are the reliable key for an early detection. The cell-based/classified/personalized diagnostic approaches are unavailable. Therefore, it was aimed to explore the expression behavior of tumor (T) cells in brain, peritoneal cavity (PC) and genomic level to deliver the hypothetical model through the metastatic events. Patients and Methods: The focal assay included protein expression (PE) by immunofluorescence in T-cells of cerebellarmeduloblastoma (CM), PC, and CTCs in a metastatic patient. The CCL2, VEGF, EGF, CD133/Cyclin E/ P21/Neuronal marker (NM), and CD45 were explored. Result: Frequency of T-cells lacking PE and the Ratio of T/CTCs in different sections of CM- tumor cells in brain and the metastatic PC revealed the diverse expression and co-expression of the involved proteins. The poor prognosis is offered upon the value of PE at T/CTCs ratio. High PE and harmonic co-expression played the influential role in the metastatic process and manner of evolution. Conclusions: Single cell- based analysis of expression and co-expression is the directive channel to unmask the heterogeneity through the metastatic process at genomic and somatic levels for providing the metastatic model. Present findings deliver the somatic/genomic ratio-based prognosis for further clinical managements.
Kleihues P, Ohgaki H. Primary and secondary glioblastomas: from concept to clinical diagnosis. Neuro Oncol 1999; 1: 44-51.https://doi.org/10.1093/neuonc/1.1.44
Lun M, Lok E, Gautam S, Wu E, Wong ET. The natural history of extracranial metastasis from glioblastoma multiforme. J Neurooncol 2011; 105: 261-273.https://doi.org/10.1007/s11060-011-0575-8
Sullivan JP, Nahed BV, Madden MW, Oliveira SM, Springer S, Bhere D, et al. Brain tumor cells in circulation are enriched for mesenchymal gene expression. Cancer Discov 2014; 4: 1299-1309.http://doi.org/10.1158/2159-8290.cd-14-0471
Kalokhe G, Grimm SA, Chandler JP, Helenowski I, Rademaker A, Raizer JJ. Metastatic glioblastoma: case presentations and a review of the literature. J Neurooncol 2012; 107: 21-27.https://doi.org/10.1007/s11060-011-0731-1
Gao F, Cui Y, Jiang H, Sui D, Wang Y, Jiang Z, Zhao J, Lin S. Circulating tumor cell is a common property of brain glioma and promotes the monitoring system. Oncotarget 2016; 7: 71330-71340.https://doi.org/10.18632/oncotarget.11114
Rossi D, Zlotnik A. The biology of chemokines and their receptors. Annu Rev Immunol 2000; 18: 217-242.https://doi.org/10.1146/annurev.immunol.18.1.217
Koch AE, Halloran MM, Haskell CJ, Shah MR, Polverini PJ. Angiogenesis mediated by soluble forms of E-selectin and vascular cell adhesion molecule-1. Nature 1995; 376: 517-519.https://doi.org/10.1038/376517a0
Sainsbury JR, Farndon JR, Sherbet GV, Harris AL. Epidermal-growth-factor receptors and oestrogen receptors in human breast cancer. Lancet 1985; 1: 364-366.
Mehdipour P, Karami F, Javan F, Mehrazin M. Linking ATM promoter methylation to cell cycle protein expression in brain tumor patients: cellular molecular triangle correlation in ATM territory. Molecular Neurobiology 2015; 52: 293-302.https//doi.org/10.1007/s12035-014-8864-9
Narayan A, Jallo G, Huisman TA. Extracranial, peritoneal seeding of primary malignant brain tumors through ventriculo-peritoneal shunts in children: Case report and review of the literature. Neuroradiol J 2015; 28: 536-539.https://doi.org/10.1177/1971400915609348
Kup PG, Nieder C, Winnekendonk G, Adamietz IA, Fakhrian K. Extracranial oral cavity metastasis from glioblastoma multiforme: A case report. Mol Clin Oncol 2016; 5: 437-439.https://doi.org/10.3892/mco.2016.991
Goodwin CR, Liang L, Abu-Bonsrah N, Hdeib A, Elder BD, Kosztowski T, Bettegowda C, Laterra J, Burger P, Sciubba DM. Extraneural Glioblastoma Multiforme Vertebral Metastasis. World Neurosurg 2016; 89: 578-582 e573.https://doi.org/10.1016/j.wneu.2015.11.061
Garzia L, Kijima N, Morrissy AS, De Antonellis P, Guerreiro-Stucklin A, Holgado BL, Wu X, Wang X, Parsons M, Zayne K. A hematogenous route for medulloblastoma leptomeningeal metastases. Cell 2018; 172: 1050-1062. e1014.
Manoranjan B, Venugopal C, McFarlane N, Doble BW, Dunn SE, Scheinemann K, Singh SK. Medulloblastoma stem cells: modeling tumor heterogeneity. Cancer Lett 2013; 338: 23-31.https://doi.org/10.1016/j.canlet.2012.07.010
Karami F, Mehdipour P. Genetic and Cellular Complexity of Brain Tumors. In :Cancer Genetics and Psychotherapy. Mehdipour P(ed), 1stedn, Springer, Cham Switzerland 2017; pp. 627-665.