Melanoma inhibitory protein (MIA1)

Abstract

MIA, also referred to as cartilage-derived retinoic acid-sensitive protein (CD-RAP), is mainly expressed in cartilaginous tissues, initiated with the advent of chondrogenesis, and is abundant throughout development of the cartilagenous skeletal system. Currently, the function of MIA in cartilage tissue is not well understood. A recent study revealed that MIA acts as a chemotactic factor for mesenchymal stem cells, and can influence the action of bone morphogenetic protein-2 (BMP-2) and transforming growth factor β3 (TGF- β3) during mesenchymal stem cell differentiation, supporting the chondrogenic phenotype while inhibiting osteogenic differentiation. MIA also specifically inhibits the attachment of melanoma cells to fibronectin and laminin, thereby masking the binding site of integrins to these extracellular matrix (ECM) components and promoting invasion and metastasis in vivo. Melanoma cells transfected with sense- and antisense MIA cDNA were analyzed in vivo in mice and hamster melanoma models for changes in their tumorigenic and metastatic potential. Enforced expression of MIA significantly increased their metastatic potential compared to control or antisense transfected cells, but it did not affect the growth rate of the primary tumor, cell proliferation or apoptosis. In addition, MIA overexpressing transfectants showed a higher rate of both tumor cell invasion and extravasation. The changes in metastatic behavior in correlation with the expression level of MIA provide evidence that upregulation of MIA during malignant transformation of melanocytic cells is causally involved in acquisition of the malignant cancer cell phenotype. Both in vivo and in vitro studies indicate that MIA enables melanoma cells to detach from some of their ECM contacts. Secretion of MIA seems to mediate an "active detachment" mechanism through which neoplastic melanocytes specifically change their attachment to components of the ECM and basement membranes to enhance their metastatic capability.
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Alternative names for this molecule: cartilage derived retinoic acid sensitive protein; CD-RAP; Cdrap; melanoma inhibatory activity; melanoma inhibitory activity 1; melanoma-inhibitory-activity; MIA; Mia1