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Insulin-like Growth Factor I Overexpression in Human Pancreatic Cancer: Evidence for Autocrine and Paracrine Roles¹

Departments of Medicine and Biological Chemistry, University of California, Irvine, California 92717 [U. B., H. F., M. Y., M. K.], and Department of General Surgery, University of Ulm, D-89075 Ulm, Germany [H. G. B.]

We assessed the potential roles of insulin-like growth factor-I (IGF-I) and the IGF-I receptor (IGF-IR) in human pancreatic cancer. IGF-I enhanced the growth of ASPC-1 and COLO-357 human pancreatic cancer cells, and this effect was significantly inhibited by a highly specific monoclonal anti-IGF-IR antibody (IR3). Both cell lines expressed mRNA transcripts for IGF-IR, and basal cell growth was significantly reduced by an IGF-IR antisense oligodeoxynucleotide. IGF-I mRNA transcripts were not detected in either cell line or in two additional pancreatic cancer cell lines. In contrast, analysis of 12 pancreatic cancers revealed a 32-fold increase (P < 0.01) in IGF-I mRNA levels by comparison with the low levels observed in the normal pancreas. By in situ hybridization, IGF-I mRNA grains were present in both the cancer cells and in the surrounding connective tissue. Six of the cancers exhibited a 4.4-fold increase in IGF-IR mRNA levels. These findings suggest that IGF-I may participate in aberrant autocrine and paracrine activation of IGF-IR in pancreatic cancer in vivo.

¹ This study was supported by USPHS Grants CA-40162 and DK-44948 awarded by the NIH (to M. K.). U. B. was supported by Deutsche Forschungsgemeinschaft, Grant Be 1762/1-1.

² To whom requests for reprints should be addressed, at Division of Endocrinology, Diabetes and Metabolism, Medical Sciences I, C240, University of California, Irvine, CA 92717.

Received 3/ 7/95. Accepted 4/ 5/95.

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