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Insulin-like Growth Factor 1 (IGF-1) Receptors, IGF-1, and IGF-2 Are Expressed in Primary Human Sarcomas¹

Samuel Lunenfeld Research Institute [A. S-O., C. O., I. L. A.], Division of Orthopedic Surgery [A. S-O., R. S. B.], and Departments of Molecular and Medical Genetics and Pathology [I. L. A.], University of Toronto [A. S-O., R. S. B., I. L. A.], Mount Sinai Hospital, Toronto, Ontario, Canada, M5G 1X5 [A. S-O., R. S. B., C. O., I. L. A.]; and Lady Davis Research Institute of the Jewish General Hospital, McGill University, Montreal, Quebec, Canada, H3T 1E2 [M. P.]

A variety of bone and soft-tissue sarcoma cell lines have been shown to express receptors for insulin-like growth factor-1 (IGF-1) and to respond mitogenically to IGF-1 in vitro. We have recently demonstrated evidence of IGF dependency in murine MGH-OGS and RIF-1 sarcomas, which express relatively high and intermediate levels of IGF-1 receptors. Overexpression of IGF-1 receptors and/or IGF ligands might, therefore, be a mechanism by which human bone and soft-tissue sarcomas obtain a proliferative advantage over normal adjacent tissues. Therefore, we evaluated 29 human sarcoma specimens for expression of IGF-1 receptor, IGF-1, and IGF-2 by competitive binding and reverse-transcription polymerase chain reaction (RT-PCR) techniques. Twelve of 29 sarcomas examined by RT-PCR and 13 of 25 examined by affinity-binding studies expressed IGF-1 receptor levels equal to or greater than levels determined in the IGF-responsive MCF-7 breast carcinoma cell line. DNA amplification of the IGF-1 receptor gene was not identified in this group of sarcomas that expressed high levels of IGF-1 receptor. Evaluation of IGF ligand expression by RT-PCR revealed that 22 of 28 sarcomas expressed IGF-1 levels comparable to or above those of the RPMI 7666 control line, and 17 of 27 sarcomas expressed significant levels of IGF-2 compared with the NCI H69 control cell line. These results suggest that autocrine/paracrine regulatory mechanisms might be responsible for the growth of some sarcomas.

¹ This work was supported by the National Cancer Institute of Canada (Grants 3372 and 3739).

² To whom requests for reprints should be addressed, at Samuel Lunenfeld Research Institute, Mount Sinai Hospital, 600 University Ave., Toronto, Ontario, Canada M5G 1X5.

Received 1/25/94. Accepted 10/31/94.

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