Characterizations of the extracellular matrix and proteinase inhibitor content of human myoepithelial tumors.
Myoepithelial tumors are intriguing low-grade neoplasms that exhibit the property of accumulating an abundant extracellular matrix. Because accumulation of an extracellular matrix represents an important exception to the rule of matrix degradation otherwise exhibited by the vast majority of human epithelial neoplasms, this study investigated the composition of this matrix to gain insight into the biological behavior of this class of neoplasms. Several different human myoepithelial tumors and their derived cell lines and xenografts were thus examined by ultrastructural, immunohistochemical, molecular, and biochemical methods. Results indicated that although the extracellular matrix of these tumors contains some basement membrane components such as laminin, nidogen, and heparan sulfate proteoglycan (8%), it is also largely cartilagenous in nature, containing large amounts of chondroitin sulfate proteoglycan (78%). In addition to extracellular matrix structural proteins, myoepithelial cells secreted relatively large amounts of proteinase inhibitors including maspin, protease nexin II, alpha1-antitrypsin, a 31-kd serine proteinase inhibitor, and TIMP-1. Immunolocalization and extraction studies further demonstrated that protease nexin II and alpha1-antitrypsin especially accumulated within the myoepithelial extracellular matrix. In addition, protease nexin II likely underwent extracellular in vivo processing to a 95-kd product retaining full proteinase inhibitor activity. These specific biochemical observations unite the classes of myoepithelial tumors, confer an anti-invasive property to their extracellular matrix, and likely contribute to their low-grade biological behavior.
Sternlicht
M D
MD
Department of Pathology, University of California, Los Angeles School of Medicine, USA.
Safarians
S
S
Rivera
S P
SP
Barsky
S H
SH
D000230:Adenocarcinoma / Q000737:chemistry; D000818:Animals; D005109:Extracellular Matrix / Q000737:chemistry*; D006023:Glycoproteins / Q000032:analysis; D006025:Glycosaminoglycans / Q000032:analysis; D006801:Humans; D051379:Mice; D009208:Myoepithelioma / Q000737:chemistry*; D009368:Neoplasm Transplantation; D011480:Protease Inhibitors / Q000032:analysis*; D019714:Tissue Inhibitor of Metalloproteinases; D014183:Transplantation, Heterologous; D014407:Tumor Cells, Cultured; D014574:Uronic Acids / Q000032:analysis
D006023:Glycoproteins; D006025:Glycosaminoglycans; D011480:Protease Inhibitors; D019714:Tissue Inhibitor of Metalloproteinases; D014574:Uronic Acids