Insulin-Like Growth Factors are Mitogenic for Human Keratinocytes and a Squamous Cell Carcinoma

• Published in: Journal of investigative dermatology Vol. 96; no. 1; pp. 104 - 110
• Main Authors: Neely, E Kirk, Morhenn, Vera B., Hintz, Raymond L., Wilson, Darrell M., Rosenfeld, Ron G.
• Format: Journal Article
• Language: English
• Published: Danvers, MA Elsevier Inc 01.01.1991; Nature Publishing
• Subjects: Biological and medical sciences; Carcinoma, Squamous Cell; Cell Division - drug effects; Cell Line; Dermatology; DNA Replication - drug effects; Humans; Insulin - pharmacology; Insulin-Like Growth Factor I - pharmacology; Insulin-Like Growth Factor II - metabolism; Insulin-Like Growth Factor II - pharmacology; Keratinocytes - cytology; Keratinocytes - drug effects; Kinetics; Medical sciences; Membrane Proteins - isolation & purification; Membrane Proteins - metabolism; Mitogens; Receptor, Insulin - isolation & purification; Receptor, Insulin - metabolism; Receptors, Cell Surface - isolation & purification; Receptors, Cell Surface - metabolism; Receptors, Somatomedin; Recombinant Proteins - pharmacology; Skin Neoplasms; Thymidine - metabolism; Tumors of the skin and soft tissue. Premalignant lesions; Human; Cell culture; Squamous cell carcinoma; Skin disease; Somatomedin C; Malignant tumor; Insulin like growth factor 2; Insulin; Gastrointestinal hormone; Polypeptide; Keratinocyte; Tumor; Mitogen; Skin; Growth factor; Biological receptor
• ISSN: 0022-202X; 1523-1747
• DOI: 10.1111/1523-1747.ep12515914

Normal adult human keratinocytes in monolayer culture and SCL-1, a skin-derived squamous-cell carcinoma cell line, were investigated for the expression of receptors for insulin- like growth factors (IGF) and insulin. As demonstrated by affinity crosslinking, radiolabeled IGF-1, IGF-2, and insulin bound specifically to both cell types. Each cell expressed type I IGF receptors, with affinity for IGF-1 > IGF-2 >> insulin. Insulin receptors, with highest affinity for insulin, were also present on both cells. However, keratinocytes and SCL-1 cells differed in 125I-IGF-2 binding. 1251-JGF-2-bound to both type I and type II IGF receptors in normal keratinocytes, but bound predominantly to membrane-associated IGF binding proteins in SCL-1. IGF-1 was slightly more potent than IGF-2 in stimulating growth of both keratinocytes and SCL-1 cells. In keratinocytes, concentrations of IGF-1 ranging from 5–100 ng/ml, and of IGF-2 from 50–100 ng/ml, resulted in a significant increase in cell number. At the maximum dose of 100 ng/ml, either IGF-1 or IGF-2 caused a 2.3-times increase in cell number. In SCL-1 cells, IGF-1 was more potent than IGF-2 or insulin at lower concentrations, but either IGF-1 or IGF-2 at the maximal concentration of 333 ng/ml stimulated a 4.7-times increase in thymidine incorporation. The stimulatory effect of insulin in SCL-1 was 10–50 times less potent than that of the IGF. The effect of either IGF on SCL-1 was completely inhibited by the type I IGF receptor antibody alphaIR-3, suggesting that both IGFs are mitogenic through the type I IGF receptor. Insulin action was partially blocked by alphalR-3, suggesting that insulin can act through both the insulin and type I IGF receptors. It thus appears that IGF-1 and IGF-2 are mitogens for normal and transformed human keratinocytes and that their actions are primarily mediated through the type I IGF receptor, whereas insulin is a mitogen through both the IGF-1 receptor and the insulin receptor.