Extracellular matrix proteins in colorectal carcinomas. Expression of tenascin and fibronectin isoforms

Abstract

Background: Interactions of tumor cells and extracellular matrix (ECM) components are crucial determinants of tumor cell spreading and metastatic activity. Particularly tenascin (TN) as a member of the adhesion modulating family of ECM and its alternatively spliced isoforms became the matter of interest in ECM changes associated with malignancy.

Experimental design: We analyzed the composition of the stromal- and basement membrane-associated ECM of colorectal adenomas and carcinomas using indirect immunofluorescence. Tenascin was investigated by immunoblot of snap frozen tumor specimens.

Results: Fibronectin (FN), TN, and chondroitin sulfate proteoglycan were the major components of the tumor stroma. Normal basement membrane components like laminin (LM), collagen type IV, and heparan sulfate proteoglycan were down-regulated. In the center of the tumor, tumor glands were surrounded by discontinuous basement membranes. At the tumor-host interface and in solid, poorly differentiated tumors, no immunoreactivity with normal basement membrane components was found. However, in cases with pericellular anti-LM staining, LM immunoreactivity was also found at the tumor-host interface. 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 matrix composition found in the present study resembles that of healing wounds and probably favors the invasive spread of tumor cells.