Reduced growth of human sarcoma xenografts in hosts homozygous for the lit mutation

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Abstract
Background and Objectives: 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 mm3 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. J. Surg. Oncol. 2002;81:75–79.

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