Tumorigenesis is a process that is mediated by a network of membrane, cytosolic and nuclear associated factors, which regulate proliferation and cell-matrix interaction through signaling cascades. The phenotype of malignant melanomas in vivo depends on the global expression of stimulatory or inhibitory factors generated in both the tumors cells and their environment. One example, Melanoma inhibitory activity (cartilage-derived retinoic acid-sensitive protein (CD-RAP), MIA) is a Src homology 3 (SH3)-like domain containing protein that is secreted from chondrocytes and malignant melanoma cells. MIA is translated as a 131-amino acid pro-form and processed into a mature 107-amino acid protein after cleavage of a secretion signal. MIA is expressed during chondrogenesis and in mature chondrocytes, suggesting that MIA is necessary for normal cartilage cell phenotype. MIA mRNA is present in carcinomas of the colon, ovary, kidney, and head/neck, and may represent a marker to monitor melanomic activity.
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