The monoclonal HBA-71 antibody modulates proliferation of thymocytes and Ewing's sarcoma cells by interfering with the action of insulin-like growth factor I.
The monoclonal HBA-71 antibody recognizes a Ewing's sarcoma associated antigen, which is also highly expressed on the cell surface of human cortical thymocytes and islets of Langerhans among normal tissues. The antibody was found to inhibit partially the growth of ES tumor cell lines and to trigger proliferation in thymocyte cultures. The influence of growth factors and the effect of the HBA-71 antibody was further investigated in the present study. The growth of ES tumor cells was demonstrated to be dependent on the presence of insulin-like growth factor I or insulin. The HBA-71 antibody (25 micrograms/ml) enhanced the growth stimulatory effect of IGF-I under serum-free conditions. The expression of the HBA-71 epitope is modulated positively by IGF-I and insulin and negatively by dexamethasone and human growth hormone in ES/PNET tumor cells and thymocytes. IGF-I either alone or in combination with HBA-71 stimulated the proliferation of thymocytes under serum-free conditions whereas in complete medium, IGF-I stimulated thymidine incorporation and the HBA-71 antibody either alone or in the presence of IGF-I showed inhibitory activity most likely due to down-regulation of the receptor. These data demonstrate the important role of IGF-I in the growth of ES/PNET tumor cells as well in the proliferative activity of HBA-71 positive normal thymocytes. The biological activity of IGF-I in malignant thymocytes, pancreas tumors, fetal muscle, brain, granulosa and Sertoli cells has been documented in the literature.(ABSTRACT TRUNCATED AT 250 WORDS)
Hamilton
G
G
I. Surgical University Clinic, University of Vienna, Austria.
Mallinger
R
R
Hofbauer
S
S
Havel
M
M
D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology*; D002455:Cell Division; D002460:Cell Line; D002675:Child, Preschool; D006801:Humans; D007223:Infant; D007328:Insulin / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology*; D008213:Lymphocyte Activation; D051379:Mice; D011956:Receptors, Cell Surface / Q000032:analysis / Q000502:physiology; D017451:Receptors, Somatomedin; D012512:Sarcoma, Ewing / Q000276:immunology / Q000473:pathology*; D013601:T-Lymphocytes / Q000276:immunology*
D000911:Antibodies, Monoclonal; D007328:Insulin; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D007335:Insulin-Like Growth Factor II