PP38. LIMITATION OF EXTERNAL LIPID SOURCES INDUCES DIFFERENTIAL PROLIFERATIVE AND MORPHOLOGICAL RESPONSES IN ADULT AND PAEDIATRIC GBM CELLS

INTRODUCTION: The tumour microenvironment of glioblastoma multiforme (GBM) demonstrates gradients in oxygen and nutrients due to an improperly formed tumour vasculature. Cancer cells obtain lipids for membrane biogenesis through anabolic cellular metabolism or internalisation of lipoproteins from the extracellular milieu. Growth rates of adult GBM cells have been demonstrated to be reduced in the absence of external lipid sources, indicating that de novo synthesis cannot generate the required lipid complement of highly proliferative cancer cells. Here, we evaluate the growth characteristics of paediatric glioma cell lines, to test the hypothesis that paediatric glioma cells demonstrate a similar growth response when cultured in lipoprotein deficient medium (LPDM) as compared to adult GBM cells. MATERIALS AND METHODS: Two paediatric GBM cell lines (KNS42 and SF188) and one paediatric grade I pilocytic astrocytoma (Res186) cell line were cultured in LPDM over a period of 7 days. Complementary experiments on adult counterparts were conducted using the U87 cell line as well as patient-derived tumour cells (GIN-8) isolated from the invasive margin of an adult GBM. Quantitative assessment of cell viability was conducted through crystal violet staining and resazurin-based PrestoBlue assays. RESULTS: Growth in LPDM reduced exponential growth rates and doubling times of KNS42 and SF188 cells after 3 days culture, reaching levels of significance (P<0.05) after 7 days. In contrast, cytostatic growth patterns were observed for Res186, U87 and GIN-8 cells after 3 days culture in LPDM. These cell lines demonstrated morphological changes reminiscent of differentiation (process elongation), whereas KNS42 and SF188 cells demonstrated a largely unaltered tumour cell membrane architecture. CONCLUSIONS: Culture of glioma cells utilising media depleted of external lipoproteins revealed an enhanced capacity of paediatric GBM cells to proliferate under acute metabolic stress compared to adult GBM and grade I paediatric glioma cells. This is suggestive of the ability of paediatric cells to utilise de novo cellular metabolism to generate lipids for proliferation, albeit at a rate that reduces doubling times. Metabolic differences between paediatric and adult cells likely portray differences at the genetic level. Growth of GBM cells under lipoprotein-deplete conditions has the potential to reveal essential metabolic pathways that will inform next-generation targeted treatment strategies.