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.