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Reduced growth of human sarcoma xenografts in hosts homozygous for the lit mutation
Author(s) -
Deitel Kevin,
Dantzer Dale,
Ferguson Peter,
Pollak Michael,
Beamer Wes,
Andrulis Irene,
Bell Robert
Publication year - 2002
Publication title -
journal of surgical oncology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.201
H-Index - 111
eISSN - 1096-9098
pISSN - 0022-4790
DOI - 10.1002/jso.10136
Subject(s) - sarcoma , in vivo , osteosarcoma , growth factor , bone sarcoma , cancer research , cell culture , medicine , receptor , insulin like growth factor , endocrinology , biology , pathology , genetics , microbiology and biotechnology
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 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. J. Surg. Oncol. 2002;81:75–79. © 2002 Wiley‐Liss, Inc.