Expression of SPARC/osteonectin/BM40 in the human gut: Predominance in thestroma of the remodeling distal intestine

SPARC is a glycoprotein of the extracellular matrix that exhibits a number of biological functions such as disruption of cell adhesion and modulation of matrix metalloprotease expression. These properties, in concert with the expression of the molecule during development, repair, and neoplastic prog ression, suggest that SPARC has an important role in remodeling in a variet y of tissues. However, the role of SPARC in the intestine is unclear since the development expression and tissular origin of SPARC in this organ appea rs to be species-dependent. As a first step to investigate the function of SPARC in the tissues of the intestine, we have analyzed its expression at t he protein and mRNA levels in the human fetal and adult small intestinal an d colonic mucosa as well as in intestinal cell models. Our results show tha t SPARC expression is differentially regulated during development and along the length of the hu man intestine. In the colon, SPARC was predominantly found at the epithelial-mesenchymal interface at the fetal stage, below det ection levels in the normal adult, but re-expressed in the stroma of coloni c tumors. In the small intestine, low levels of SPARC expression were obser ved at an early stage of morphogenesis (between 9 and 11 weeks) but express ion was not detected at subsequent developmental stages nor was it induced in the mucosa of Crohn's disease. While SPARC appeared to be produced mainl y by mesenchymal and stromal cells in the intact intestine it was not detec ted in colon cancer cells. Taken together, these results indicate that SPAR C is subject to an onco-fetal pattern of expression in the stroma of the co lonic mucosa while its expression is much more restricted in the small inte stine, suggesting a differential involvement of this molecule in the extrac ellular matrix remodeling occurring along the length of the developing and diseased human intestinal mucosa. J Cell Biochem 81:463-476, 2001. (C) 2001 Wiley-Liss, Inc.