Since Coman in 1944 observed that decreased adhesiveness is a characteristic of malignant cells and Grobstein 10 years later demonstrated that epithelial and mesenchymal cells influence each other when separated by a cell-impermeable filter, components of the extracellular matrix have been suspected of playing an active role in
cancer growth.
Breast cancer is frequently characterized by an increase in connective tissue fibroblastic cells and extracellular matrix, the nature and molecular composition of which is gradually being revealed. Two of the most studied and hence best known components of extracellular matrix are
fibronectin and
laminin. They are called adhesive or structural
glycoproteins, because they are part of the stabilizing scaffold, which links connective tissue cells to each other (
fibronectin) and connects connective tissues with parenchymatous cells via basement membranes (
laminin). Both molecules harbour a variety of specific binding sites, which allow them to participate actively in basic dynamic processes such as cell modulation, -attachment, -spreading and -migration.
Tetranectin is a recently discovered
protein of human plasma and nucleated cells, which is suspected of participating in tissue degradation and proteolysis through its specific binding to
plasminogen, a member of the
plasminogen activation system. The immunohistochemical studies of
fibronectin,
laminin and
tetranectin, on which this thesis is based, were undertaken in order to investigate if qualitative or quantitative changes of these
proteins between benign and malignant breast tissue would reflect the net effect of the different inherent characteristics of
breast cancer cells known from experimental studies (i.e. unanchored growth, proteolysis, metastatic spread and de novo production of extracellular matrix components). A significant increase in stromal
fibronectin was a consistent finding in all infiltrating
carcinomas, permitting the discrimination between such
tumors and benign proliferative lesions as well as between
carcinomas with a sarcomatoid appearance and true
breast carcinomas. However, as a possible consequence of
tumor heterogeneity this stromal reactivity pattern varied and tended to disappear focally along the invasive front of
tumors with a high metastatic potential. A concurrent increase in the
tumor cell expression of FN was found in poorly differentiated
tumors, which could either be due to increased
fibronectin production by the more anaplastic
tumor cells or internalization of exogenous
fibronectin bound to its receptor. Whereas most of the extracellular
fibronectin in
breast cancer is thought to be produced by the stromal fibroblasts, extracellular
laminin is considered a product of the epithelial
tumor cells.(ABSTRACT TRUNCATED AT 400 WORDS)