Influence of IGF-IR stimulation or blockade on proliferation of human renal cell carcinoma cell lines.
Several tumors secrete insulin-like growth factors (IGFs) for autocrine growth stimulation and protection from apoptosis. However, the mechanisms responsible for tumor growth in renal cell carcinoma (RCC) are unclear. In this study the biological role of exogenous IGFs in two malignant RCC cells (Caki-2 and SK-RC-52) were investigated in vitro, and compared to the breast cancer cell line MCF-7. IGFs but not the related epidermal growth factor stimulated both RCC cell lines. Caki-2 expressed higher levels of IGF-IR and proliferated more vigorously to added IGF-I, IGF-I analogues des(1-3)IGF-I, LongR3IGF-I and IGF-II compared to SK-RC-52. Neutralizing IGF-IR antibodies reduced the IGF driven proliferation in both cell lines. Interestingly, soluble IGF-I receptor resulted in strong growth inhibition of SK-RC-52, while no marked effect on Caki-2 was observed. Moreover, Caki-2 expressed a broad panel of IGFBPs, while SK-RC-52 more selectively secreted high levels of IGFBP-3. Exogenous IGFBP-3 strongly inhibited IGF-I driven proliferation in SK-RC-52, but worked in synergy with IGF-I in Caki-2. Both the IGF-IR and IGFBP-3 were present in respectively 4/4 and 4/8 human malignant renal tissues. In light of this and with the functional data presented in this study, interference with this growth factor system may provide a novel therapeutic approach in renal cancer therapy.
Rosendahl
Ann
A
Active Biotech Research AB, Department of Cellular and Molecular Biology, PO Box 724, S-220 07 Lund, Sweden.
Forsberg
Göran
G
D001943:Breast Neoplasms / Q000235:genetics* / Q000473:pathology*; D002292:Carcinoma, Renal Cell / Q000235:genetics* / Q000473:pathology*; D049109:Cell Proliferation; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D007150:Immunohistochemistry; D007334:Insulin-Like Growth Factor I / Q000494:pharmacology; D007335:Insulin-Like Growth Factor II / Q000494:pharmacology; D007680:Kidney Neoplasms / Q000235:genetics* / Q000473:pathology*; D017451:Receptors, Somatomedin / Q000096:biosynthesis* / Q000378:metabolism; D014407:Tumor Cells, Cultured
D017451:Receptors, Somatomedin; D007334:Insulin-Like Growth Factor I; D007335:Insulin-Like Growth Factor II