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Relationship between Extracellular Matrix Interactions and Degree of Differentiation in Human Colon Carcinoma Cell Lines¹

Laboratory of Cancer Biology, New England Deaconess Hospital and Harvard Medical School, Boston, MA 02115

Human colon carcinoma cell lines that vary in their degree of differentiation were examined for their ability to interact with extracellular matrix components. For this purpose, established cell lines were classified on the basis of several criteria that relate to degree of differentiation. These criteria include histology of the original tumor, histology of xenografts, in vitro morphology, and carcinoembryonic antigen expression. On this basis, the cell lines used were either moderately well or poorly differentiated. The poorly differentiated cell lines adhered to surfaces coated with laminin or reconstituted basement membrane extract (Matrigel) to a significantly greater extent than the moderately well differentiated lines with the exception of one moderately well differentiated line that was derived from a highly aggressive signet ring cell carcinoma. In addition, the poorly differentiated cell lines exhibited considerable spreading on laminin and Matrigel after adherence that was not evident for the moderately well differentiated lines. The adherence of these cell lines on fibronectin-coated surfaces did not correlate as well with differentiation although, in general, poorly differentiated cell lines adhered better than moderately well differentiated lines. None of the cells that adhered to fibronectin exhibited the extensive spreading seen on laminin. The specificity of tumor cell interactions with extracellular matrix glycoproteins was examined using synthetic peptides which correspond to sequences within these proteins that are recognized by cell surface receptors. The pentapeptide YIGSR-NH₂ significantly inhibited the adherence and spreading of the tumor cell lines on laminin, but not on fibronectin. The peptide RGDS, however, did not inhibit tumor cell interactions with laminin although it did inhibit their interactions with fibronectin. Thus, the interactions of colon carcinoma cells with laminin and fibronectin are probably mediated by separate receptors. Taken together, the data demonstrate that cells derived from colon carcinomas exhibit considerable variation in their ability to interact with extracellular matrix components, and that this variability is related to the degree of differentiation of original tumor.

¹ This work was supported by NIH Grant CA44704. Dr. Mercurio is the recipient of an American Cancer Society Junior Faculty Research Award.

² To whom requests for reprints should be addressed, at New England Deaconess Hospital, Laboratory of Cancer Biology, 50 Binney Street, Boston, MA 02115.

Received 6/10/88. Revised 10/24/88. Accepted 11/ 1/88.

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