Reduced growth of human sarcoma xenografts in hosts homozygous for the lit mutation.
OBJECTIVE
Prior studies have shown that sarcoma growth can be stimulated by insulin-like growth factor-I (IGF-I). To extend this line of research, we carried out in vivo growth studies of primary human sarcoma in immunosuppressed control and IGF-I-deficient mice.


METHODS
Human sarcoma specimens (one osteosarcoma and seven soft tissue sarcomas) were harvested in the operating room and implanted in immunosuppressed mice. Second-generation sarcomas were transplanted to control (GH replete lit/+ mice) and to experimental (GH/IGF-I-deficient lit/lit) animals. When tumors reached 1,000 mm(3) in one group, average tumor size was compared in the two groups. IGF-I receptor expression was measured by RT-PCR and IGF-I receptor binding sites were assayed by radiolabeled IGF-I.


RESULTS
Five of eight sarcomas demonstrated reduced growth in the GH/IGF-I-deficient lit/lit animals. In four of the five sarcomas that demonstrated growth inhibition, IGF-R was elevated relative to placenta or a positive control cell line (MCF-7, which is known to be responsive to IGF-I in vitro and in vivo). In three of the five sarcomas that demonstrated growth suppression, IGF-R was elevated twofold after implantation in the experimental IGF-I-deficient animals.


CONCLUSIONS
The GH-IGF axis may be an important stimulator of tumor growth in sarcomas. These experiments suggest that IGF suppression may inhibit sarcoma growth in vivo.
D000818:Animals; D001859:Bone Neoplasms / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D006801:Humans; D051379:Mice; D016513:Mice, SCID; D009154:Mutation; D009368:Neoplasm Transplantation; D017526:Receptor, IGF Type 1 / Q000235:genetics / Q000378:metabolism*; D018013:Receptors, Neuropeptide / Q000235:genetics / Q000378:metabolism*; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000235:genetics / Q000378:metabolism*; D012509:Sarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*
D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D017526:Receptor, IGF Type 1; C048250:somatotropin releasing hormone receptor