ROLE OF CELL SURFACE CARBOHYDRATES IN TUMORIGENICITY
RIPKA, JAMES EDWARD
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Changes in carbohydrates of the plasma membrane have been implicated in both tumor formation and metastasis. In order to investigate a direct correlation between the altered expression of cell surface carbohydrates and malignancy, lectin-resistant (LecR) Chinese hamster ovary (CHO) glycosylation mutants were examined for their abilities to form tumors in nude mice. To expand the series of mutants available for these studies, new glycosylation mutants were sought. Four new pea lectin-resistant CHO lines were isolated. Two mutants termed Lec13 and Lec13A were shown to belong to the same recessive complementation group and two mutants termed LEC14 and LEC18 were shown to behave dominantly in somatic cell hybrids. The biochemical defect in Lec13 and Lec13A cells was localized to the first enzyme activity of the GDP-mannose GDP-fucose conversion pathway, namely GDP-mannose 4,6-dehydratase. Whereas, Lec13 showed no detectable GDP-mannose 4,6-dehydratase activity, the Lec13A mutant had partial enzyme activity.;Three of the new mutants, Lec13, Lec13A and LEC14, and a panel of twelve, previously-isolated, glycosylation-defective CHO mutants were examined for their tumorigenic and metastatic capacities following subcutaneous injection into nude mice. Most of the glycosylation mutants displayed similar or slightly decreased tumorigenicity compared to parental CHO cells. Neither parental CHO nor any of the mutants were observed to metastasize. However, independent isolates of one mutant type, Lec9, showed a dramatic reduction in tumor formation. The carbohydrates expressed at the surface of Lec9 cells are implicated (directly or indirectly) in their loss of tumorigenicity since revertants for lectin-resistance were able to form tumors. Finally, (gamma)-irradiation of nude mice allowed the formation of tumors by Lec9 cells suggesting that an irradiation-sensitive host cell might be responsible for the reduced tumorigenicity of Lec9 mutants.