Isozyme pattern in serially xenotransplanted childhood tumors.

Growth rate, histological course, and polymorphic enzyme pattern (glucose 6-phosphate dehydrogenase, glucose phosphate isomerase, and phosphofructokinase) were studied in eight childhood tumors xenotransplanted serially to nude mice. The growth rate of these tumors (three nephroblastomas, one hypercalcemic renal tumor, three rhabdomyosarcomas, and one malignant histiocytosis) appeared stable for any one particular tumor line. The time interval between two grafts varied from 1 to 3 weeks to 1 to 2 months in correlation with the clinical course of each malignant process. Histological changes were mostly in relation with a progressive dedifferentiation of the grafts. Immunoneutralization of glucose-6-phosphate dehydrogenase and glucose phosphate isomerase made possible the quantification of the stroma reaction in the grafts. A series of ten passages showed the amount of stroma to be constant for a given tumor type but variable from one tumor type to another, except for the malignant histiocytosis which showed an increase in stroma constituent after the sixth passage. One nephroblastoma tumor line showed, during the third passage, a sudden acceleration in the growth rate and complete transformation of the histological and isozymic patterns, which were interpreted as being the result of a murine lymphoma. The fibroblastic form of phosphofructokinase increased in every tumor line, whatever the tumor type. This change may be linked to a progressive dedifferentiation during the passage.