Differential Production of High Molecular Weight Sulfated Glycoproteins in Normal Colonic Mucosa, Primary Colon Carcinoma, and Metastases

Abstract

Sulfated macromolecules synthesized in tumor and mucosa tissues derived from colorectal cancer patients were labeled with [³⁵S]sulfate and separated into two fractions on DEAE-Sephacel: the slightly acidic peak (peak I) was eluted with 0.2 m NaCl and the highly acidic peak (peak II) was eluted with 0.5 m NaCl. A total of 40 specimens, which included primary colon cancer, liver metastases, and normal mucosa obtained at surgery (16 patients), were examined regarding the amount of peak I and peak II. The amount of peak I significantly decreased in the order of normal mucosa > primary tumors > metastases, while the amount of peak II did not significantly change among the tissues. Peak I was mostly resistant to chondroitinase ABC and nitrous acid treatment under acidic conditions, whereas combined chondroitinase-sensitive materials and nitrous acid-sensitive materials were greater than 80% of the radioactivity in peak II. The major radioactive component of peak I migrated at a position corresponding to M_r > 300,000 by sodium dodecyl sulfate-polyacrylamide gel electrophoresis and became M_r < 40,000 after alkaline borohydride treatment. The major component of peak I was likely to be a sulfated glycoprotein containing sulfate groups on alkaline labile carbohydrate chains. Peak II consisted of a mixture of heparan sulfate proteoglycans and chondroitin sulfate proteoglycans. Differential incorporation of [³⁵S]sulfate into peak I among normal mucosa, primary colon carcinoma, and colon carcinoma metastasis was observed. Therefore, decreased peak I production may be a biochemical change associated with colorectal cancer progression and metastasis.