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Expression of Adrenomedullin and Its Receptor in Normal and Malignant Human Skin: A Potential Pluripotent Role in the Integument

Cell and Cancer Biology Department (A.M., T.W.M., M.J.M., F.C.), Medicine Branch, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, 9610 Medical Center Drive, Rockville, Maryland 20850; Agricultural Research Service (T.H.E.), United States Department of Agriculture, Beltsville, Maryland 20705; Department of Pathology (C.M.), H. Lee Moffitt Cancer Center, Tampa, Florida 33612; and Department of Obstetrics and Gynecology (C.J.M.), Uniformed Services University of Health Sciences, Bethesda, Maryland 20814

Address all correspondence and requests for reprints to: Dr. Alfredo Martínez, Cell and Cancer Biology Department, Division of Clinical Sciences, National Cancer Institute, National Institutes of Health, 9610 Medical Center Drive, Room 300, Rockville, Maryland 20850. E-mail: martineza{at}bprb.nci.nih.gov

Adrenomedullin (AM) is a multifunctional peptide involved in a variety of physiological functions, including growth regulation and antimicrobial activity. We have determined by immunohistochemistry and in situ hybridization that AM and its receptor are present in all the epithelial cells of the normal skin, including keratinocytes of the epidermis and hair follicles, as well as cells of the glands and secretory ducts. We also have detected AM in the sweat, by RIA. In addition, AM and its receptor were found in skin tumors of different histologies. The presence of AM and its receptor in normal and neoplastic skin was confirmed by RT-PCR and Western blot analysis performed on cell extracts from human skin cell lines. Radiolabeled AM bound to specific sites in cultured cells with a K_d of 9 nM. This binding was blocked by the addition of cold AM but not by related peptides such as AM 22–52, pro-AM 20 N-terminal peptide, calcitonin gene-related peptide, calcitonin gene-related peptide 8–37, or amylin. Finally, exposure to synthetic AM resulted in an increase of thymidine intake by skin cells. These results implicate AM as a potential player in skin defense against infectious microorganisms and as a possible autocrine growth factor in normal skin physiology and tumor development.

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