The Endocytic Collagen Receptor, uPARAP/Endo180, in Cancer Invasion and Tissue Remodeling
uPARAP/Endo180 is a constitutively recycling endocytosis receptor of 180 kDa. It is a type-1 membrane protein and includes an N-terminal Cys-rich domain followed by a fibronectin type-II domain, eight C-type lectin-like domains, a transmembrane segment, and a small cytoplasmic domain. The receptor binds and internalizes collagen, which is then directed to lysosomal degradation. The internalization efficiency increases when the collagen is in a gelatin-like state and, in line with this notion, the uptake of defined 1/2 and 3/4 collagen fragments is more efficient than the internalization of intact collagen. Thus, uPARAP/Endo180 most likely has a preferential role in the clearance of precleaved collagen, occurring after the initial attack of a collagenolytic MMP. Mesenchymal cell types such as fibroblasts, osteoblasts, some endothelial cells, and some macrophages express uPARAP/Endo180, with a strong expression in areas with dominant collagen turnover, such as developing bone. PyMT mice, which develop genetically induced, invasive mammary tumors, have reduced tumor growth and increased tumor collagen content when uPARAP/Endo180 is absent due to gene inactivation. Cancer cells have not been found to express uPARAP/Endo180 but some of the same cell types that express the receptor in healthy tissue show a strong increase in expression when they take part in the stroma that surrounds the cancer islets in some invasive cancers. Thus, in some situations involving invasive growth, collagen clearance by uPARAP/Endo180 is likely to take active part in the outgrowth and escape of cancer cells from a confined tissue compartment.
After the submission of this manuscript, it has been reported that uPARAP/Endo180 is expressed in basal-like breast cancer cells (Wienke, D. et al. (2007) Cancer Res. 67:10230–10240).
KeywordsMannose Receptor Collagen Degradation Collagen Binding Collagen Fragment Lysosomal Cysteine Protease
Unable to display preview. Download preview PDF.