Effects of Surgical Excision and Radiation on Medulloblastoma Cell Invasiveness

Abstract

In children, brain cancers can be particularly devastating; and medulloblastoma (MB), a primitive tumour of neuroectodermal origin, is among the most common. Rare in adults [1][2][3][4][5] , these tumours generally account for between 20 and 40% of paediatric intracranial malignancies worldwide [6][7][8][9][10][11][12] , and have an incidence of approximately 1-7 per million, depending upon the population studied and how medulloblastoma and the base populations are defined 11,[13][14][15][16] . They are especially common among preschoolers 17,18 , even among infants who are less than 18 months-of-age 19,20 . Outcomes in paediatric medulloblastoma patients, relative to those with most other childhood malignancies, tend to be poor, with five-year survival rates in ABSTRACT: Objectives: Surgical resection and adjuvant radiation are mainstays of medulloblastoma (MB) patient management. We utilized a novel 3-dimensional assay to identify how (a) radiation, (b) excision of the primary tumour aggregate, and (c) both treatments combined influence MB cell invasiveness. Methods: Five MB cell lines (UW228-1, 2 and 3; Daoy, and Madsen) were implanted onto a 3-dimensional, type I collagen gel assay to assess tumour invasion distance over five days, in response to (1) needle-assisted excision of the central cell aggregate; (2) pre-exposure to single-dose and fractionated dose irradiation in doses from 6-25 and 8-24 Gy, respectively; and (3) excision plus either single-dose or fractionated radiation. Results: Within hours, individual MB cells detached from the surface of the cell aggregates and invaded the collagen matrix, to distances up to 1200 µm and at rates up to 300 µm daily. The UW228-1 cell line was less invasive than the other cell lines and was dropped from further analysis. In the four remaining lines, a dosedependent decline in tumour invasiveness was identified, both for single-dose and fractionated radiation, which achieved statistically decreased invasion distances at higher doses, especially of fractionated irradiation. Excision of the central tumour aggregate tended towards exerting a late effect on cell invasion, but exerted no significant influence on the radio-sensitivity of residual cells. Conclusions: Both single-dose and fractionated dose irradiation appear to inhibit MB cell invasiveness in a dose-dependent manner, whereas excision of the central cell aggregate exerts no effect on residual invading cells. RÉSUMÉ: Effets de l'excision chirurgicale et de l'irradiation sur le caractère envahissant du médulloblastome.Objectifs : La résection chirurgicale et la radiothérapie sont le traitement de base du médulloblastome (MB). Nous avons utilisé une nouvelle méthode d'analyse tridimensionnelle pour identifier comment l'irradiation, l'excision de la tumeur primaire et les deux traitements combinés influencent le caractère envahissant des cellules du MB. Méthodes : Cinq lignées cellulaires de MB (UW228-1, 2, 3, Daoy et Madsen) ont été implantées dans un gel de collagène de type I tridimensionnel pour évaluer la...

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