Gliomas are known to express over a hundred
antigens, and no doubt make many more unknown
antigens. Major categories of
glioma cell
antigens include glial
antigens, ECM
antigens, muscle
antigens, melanoma antigens, "tumor-specific"
antigens, and cellular proliferation
antigens. A strikingly low number of cultured
gliomas express glial
antigens. They commonly express not only ectodermal, but also mesenchymal ECM
antigens.
Tumor-specific
antigens have been an elusive goal of neuro-oncologists, but there are bright new prospects in need of further study. These include direct screening of hybridoma supernatants on
glioma tissue and targeting
glycolipids,
glycoproteins, and
oncogene products. Cellular proliferation
antigens will become increasingly important in predicting prognosis of
gliomas. Proliferation
antigens of cultured
gliomas are under intense scrutiny at present. The extent and evolution of antigenic heterogeneity of neoplastic cells in
gliomas raise basic
biologic questions with profound clinical ramifications. Individual
glioma cell lines may generate more than 30 subtypes of cells with minor to major differences in
antigen expression. These include expression of
antigens representing multiple different cell lineages. Mesenchymal drift is the tendency of
gliomas to progressively lose glial and gain mesenchymal features. Models of in vivo mesenchymal drift occur in
glioma cell culture where mechanisms are more easily investigated than in situ. Neither exogenous
protein absorption nor fibroblast overgrowth explain the phenomenon. Cells with the mesenchymal marker,
fibronectin, overgrow GFAP-positive cells during explanation of
gliomas. Many of these
fibronectin-positive cells express cytologic and growth characteristics of
neoplasia. The source of these cells is unknown. A leading candidate for the source of these neoplastic
fibronectin-positive cells is the proliferation of vascular and mesenchymal cell elements of
glioma tissue commonly called "endothelial proliferations". However, these elements in tissue do not display the same abnormalities of
neoplasia as the
fibronectin-positive cells in culture. Understanding this "tissue/explant paradox" may solve the conundrum of mesenchymal drift. In the absence of a counterpart in tissue of these neoplastic
fibronectin-positive cells so abundant in
glioma cell cultures, mechanisms of mesenchymal drift other than overgrowth of neoplastic mesenchyme must be considered. The occurrence of "dual cells" which express antigenic markers of entirely different cellular lineages suggests the possibility that neoplastic glia generate mesenchymal drift by altered gene expression. Various studies which suggest the capacity of cultured
gliomas to alter phenotypic expression of their genes are critically examined and their relevance to mesenchymal drift discussed.(ABSTRACT TRUNCATED AT 400 WORDS)