Invasive properties of primary pediatric neoplasms in vitro
Bogenmann, E.; Mark, C.; Isaacs, H.; Neustein, H.B.; De Clerck, Y.A.; Laug, W.E.; Jones, P.A.
Cancer Research 43(3): 1176-1186
1983
ISSN/ISBN: 0008-5472 PMID: 6297720 Document Number: 211602
Primary solid tumors [Wilm's tumor, neuroblastoma, brain tumor, Ewing's sarcoma, rhabdomyosarcoma, osteogenic sarcoma, carcinoma] were mechanically and/or enzymatically disassociated, and the resulting suspensions of single cells and small clumps of cells were seeded onto 3 different substrates, i.e., tissue culture plastic, rat smooth muscle cells (SMC), and SMC-derived extracellular matrix. Tests of the relative effectiveness of these substrates in supporting the survival and/or growth of 10 different neoplasms demonstrated that only 2 explants remained viable for longer than 2 wk when seeded onto tissue culture plastic while 9 of the 10 survived on biological substrates for 1 mo. or longer. Tissue culture plastic was a poor substrate for primary pediatric neoplasms. In general, more than 80% of the most common solid neoplasms in childhood (brain tumor, neuroblastoma, renal tumor, rhabdomyosarcoma, osteogenic sarcoma and Ewing's sarcoma) routinely survived or grew in long-term cultures when cultured onto SMC or their matrix. Both substrates were effective in promoting survival and/or growth; however, cells of neuroblastomas and certain brain tumors showed a preference for a living smooth muscle substrate. Tumor cells maintained their characteristic cellular and subcellular morphology when compared with the histology of the in vivo neoplastic lesions. Light microscopy and EM of selected neoplasms cultured on SMC for various time periods demonstrated areas of distinct cellular invasion and/or partial destruction of the SMC multilayers which correlated with the invasive potentials of the neoplasms in patients. Invasion and destruction of the SMC were also noticed with quiescent tumor cell cultures, indicating that growth was not a necessary property of invasion. Several neoplasms were also capable of the degradation of connective tissue proteins as indicated by the hydrolysis of radiolabeled SMC matrices, but simple correlations between the extent of matrix degradation and invasive ability could not be drawn. The culture system described consistently provided for the survival and/or growth of the most common pediatric tumors for long periods of time. Basic biological properties of primary tumors, e.g., growth, invasive potentials and differentiation capabilities, could be investigated routinely.