MGSA - Melanoma growth stimulatory activity

Abstract

This chapter discusses tissues sources, regulation of expression, and structure of melanoma growth stimulatory activity (MGSA). MGSA was originally found as a mitogenic polypeptide secreted by human melanoma cells. The MGSA/GRO-α gene product has potent chemotactic, growth regulatory, and transformative functions. The tissue sources include monocytes, human nasal and bronchial epithelium, bronchoalveolar macro-phages, rat anterior pituitary cells, neutrophils, endothelial cells, epidermal keratinocytes, and different tumor cells such as melanoma, benign intradermal, and dysplastic nevi. Basal and cytokine-induced expression of MGSA/GRO-α requires at least three transcription factors, Sp, NF-κB, and HMGI(Y) in the melanoma cell line Hs294T. MGSA is found in the cytoplasmic granules in the melanosomes in metastatic melanoma patients. The MGSA monomer contains an N-terminal loop, a three-stranded antiparallel β-sheet arranged in a Greek key conformation, and a C-terminal α-helix. It is found that at the quaternary level the difference between IL-8 and MGSA results from differing angles between the β-strands which form the dimer interface, and is manifested as a different interhelical separation.