Clonal sublines of rat neurotumor RT4 and cell differentiation: II. A conversion coupling of tumorigenicity and a glial property

RT4 is a neurotumor induced by ethylnitrosourea injection of a newborn BDIX rat. We demonstrated previously that heterogeneity in early cultures of RT4 tumor cells can be regularly reproduced in cultures of clonal stem cells (cell type conversion). Our previous studies included morphology, differentiation of neural properties, and chromosome number of “tumor-derived” and “stem cell-derived” differentiated cells. In this paper, these two sets of differentiated cells were examined further for three additional parameters, all of which are related to malignancy. The stem cell (AC) and one type of differentiated cell (D) cause tumors when subcutaneously injected into syngeneic animals, while the other two types (B and E) do not. The amounts of a 250,000 molecular weight cell surface protein, which is probably equivalent to LETS protein (large external transformation-sensitive protein) of hamster and mouse, and the levels of plasminogen activator were examined as possible markers of malignancy. As anticipated, nontumorigenic cells generally have a large amount of the 250,000 molecular weight cell surface protein and are low in plasminogen activator activities, whereas the reverse is true for tumorigenic cells. This supports the idea that B and E cells are nontumorigenic revertants. The cell type conversion phenomenon of RT4 neurotumor and the differentiation of mouse teratoma and myeloid leukemic cells share a number of similarities, but differ in that differentiated RT4 cells can propagate in vitro even after loss of tumorigenicity. The concomitant expression of tumorigenicity and the S100 protein production of the D cell, or of nontumorigenicity and B and E cell differentiation upon the conversion of the stem cell, may suggest a regulational coupling between the tumorigenicity and the expression of a glial protein (S100 protein) in D cells.