FROM RODENT GLIAL PRECURSOR CELL TO HUMAN GLIAL NEOPLASIA IN THE OLIGODENDROCYTE-TYPE-2 ASTROCYTE LINEAGE

With only a few exceptions, the precursor cells representing the norma l counterparts of human tumours are unknown. The comparative lack of i nformation about the lineages involved in tissue development, and diff iculties in growing many human tumors in a manner suitable for cellula r biological analysis, together often make it difficult to study the d ifferences between normal and tumor cells and to develop many of the m odel systems that would be useful in the study of human cancer. By app lying techniques previously utilized to study glial progenitor cells, we have isolated a human glioblastoma multiforme (GBM)-derived populat ion that expresses many properties otherwise uniquely expressed by oli godendrocyte-type-2 astrocyte (O-2A) progenitor cells. Hu-O-2A/Gb1 (fo r Human O-2A lineage Glioblastoma number 1) cells responded to similar mitogens and differentiation modulators as rodent O-2A progenitors, a nd generated cells with features of precursor cells, oligodendrocytes and astrocytes. Moreover, H-1-NMR analysis of amino acid composition d emonstrated a striking conservation of types and quantities of free am ino acids between the human tumour cells and the rodent primary cells. Hu-O-2A/Gb1 cells represent the first human glioma-derived population for which unambiguous lineage assignment has been possible, and our r esults indicate that the human O-2A lineage can contribute to one of t he most malignant of glial tumours. In addition, the highly diagnostic H-1-NMR spectrum expressed by Hu-O-2A/Gb1 cells raises the possibilit y of eventual non-invasive identification of tumors of this lineage. ( C) 1995 Wiley-Liss, Inc.