EXTRACELLULAR-MATRIX PROTEINS IN COLORECTAL CARCINOMAS - EXPRESSION OF TENASCIN AND FIBRONECTIN ISOFORMS

BACKGROUND: Interactions of tumor cells and extracellular matrix (ECM) components are crucial determinants of tumor cell spreading and metas tatic activity. particularly tenascin (TN) as a member of the adhesion modulating family of ECM and its alternatively spliced isoforms becam e the matter of interest in ECM changes associated with malignancy. EX PERIMENTAL DESIGN: We analyzed the composition of the stromal- and bas ement membrane-associated ECM of cololrectal adenomas and carcinomas u sing indirect immunofluorescence. Tenascin was investigated by immunob lot of snap frozen tumor specimens. RESULTS: Fibronectin (FN), TN, and chondroitin sulfate proteoglycan were the major components of the tum or stroma. Normal basement membrane components like laminin (LM), coll agen type IV, and heparan sulfate proteoglycan were down-regulated. In the center of the tumor, tumor glands were surrounded by discontinuou s basement membranes. At the tumor-host interface and in solid, poorly differentiated tumors, no immunoreactivity with normal basement membr ane components was found. However, in cases with pericellular anti-LM: staining, LM immunoreactivity was also found at the tumor-host interf ace. An alternatively spliced isoform of TN with a molecular weight of 330 kDa was found in seven of 15 carcinomas. In four of these cases, an alternatively spliced isoform of FN containing the ED-B segment was present. CONCLUSIONS: The coexpression of alternative splicing of FN and TN suggests that there may be common regulation mechanisms. The ma trix composition found in the present study resembles that of healing wounds and probably favors the invasive spread of tumor cells.