Insulin-like growth factor I (IGF-I) activity has been reported to be produced by several human cancers. Identification of RNAs transcribed from the IGF-I gene has been complicated by the detection of multiple hybridizing bands on Northern analysis. To determine if any of these RNAs are transcribed from the IGF-I gene, we have used a sensitive and specific ribonuclease (RNAse) protection assay for IGF-I. We have also studied the breast cancer tissue expression of IGF-I using in situ hybridization histochemistry. We have found no IGF-I mRNA in breast (zero of 11) or colon cancer (zero of 9) cell lines; both of these tumors have been previously reported to express IGF-I mRNA. However, three of three neuroepithelioma and one of two Ewing's sarcoma cell lines express IGF-I mRNA; therefore, in these tumors IGF-I may be an autocrine growth factor. In contrast to breast cancer cell lines, RNA extracted from breast tissues has easily detectable IGF-I mRNA. In situ hybridizations show that IGF-I mRNA is expressed in the stromal cells, and not by normal or malignant epithelial cells. These findings suggest that although IGF-I is not produced by breast epithelial cells it may function as either a paracrine stimulator of epithelial cells or an autocrine stimulator of stromal cells.

Expression of insulin-like growth factor I (IGF-I) mRNA by some tumor cell lines of neuroectodermal origin has been described. To further explore the significance of IGF-I mRNA expression in these tumors, a more extensive analysis was performed. Most (9 of 10) neuroectodermal tumor cell lines with a t(11;22) translocation (primitive neuroectodermal tumor IPNETI, Ewing's sarcoma, esthesioneuroblastoma) expressed IGF-I mRNA, whereas 0 of 15 cell lines without the translocation (PNET, neuroblastoma) expressed IGF-I. Furthermore, inasmuch as all neuroblastoma (12 of 12) cell lines examined expressed IGF-II RNA, the pattern of IGF expression could distinguish between these closely related tumors. CHP-100, a PNET cell line with the t(11;22) translocation, was shown to secrete both IGF-I protein and an IGF binding protein, IGFBP-2. This cell line also expressed the type I IGF receptor mRNA, and blockade of this receptor by a monoclonal antibody (aIR3) inhibited serum-free growth. These data demonstrate that IGF-I expression is a property of neuroectodermal tumors with a t(l 1;22) translocation and that interruption of an IGF-I autocrine loop inhibits the growth of these tumor cells.

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