Effects of Surgical Excision and Radiation on Medulloblastoma Cell Invasiveness

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 dose-dependent 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.