Characterization of insulin, insulin-like growth factors I and II, and growth hormone receptors on human leukemic lymphoblasts

Abstract

Receptors for insulin, insulin-like growth factors I and II (IGF-I and IGF-II), and human GH were studied in 6 T- and 12 B-lymphoblast cell lines isolated from patients with lymphoid malignancies. These cell lines have been maintained in continuous culture with stable chromosome, immunophenotype, and enzyme characteristics for an 8- to 21-month period. Four of 6 T-cell lines expressed IGF-I, but not insulin, receptors. One T-cell line bound only insulin, and 1 T-cell line bound both hormones. Conversely, 9 of 12 B-cell lines had insulin, but not IGF-I, receptors. Two of these lines bound both hormones, and 1 line did not bind either hormone. IGF-II binding was less than 1.5%/10 million cells for all lines and was less than 1% for 13 of the 18 lines. Specific binding of GH was undetectable in all cell lines. Time, temperature, and pH dependence of peptide binding were characterized for the T-cell IGF-I receptor and the B-cell insulin receptor and were consistent with previously described models for these receptors. Sodium dodecyl sulfate-polyacrylamide gel electrophoresis of the cross-linked receptors revealed an apparent mol wt greater than 300K unreduced and a 130K binding subunit after dithiothreitol reduction for both the T-cell IGF-I and the B-cell insulin receptor. These cell lines thus provided a unique opportunity for the study of growth factor receptors in fully characterized clonal populations of human lymphoblasts. We conclude that specific receptors for IGF-I and insulin are present on T- and B-lymphoblasts; divergence of these receptors appears to be a characteristic of lymphoblasts, since T-cells preferentially expressed IGF-I receptors and B-cells expressed insulin receptors; and IGF-II binding was relatively low, while specific GH binding was undetectable on both T- and B-lymphoblasts. These results suggest that insulin and IGF-I may play a role in lymphocyte differentiation and metabolism.