Up-regulation of macrophage wnt gene expression in adenoma-carcinoma progression of human colorectal cancer

Defects in the APC-beta-catenin pathway are common in colon cancer. We inve stigated whether aberrant regulation of upstream ligands stimulating this p athway occur in colon cancer. Using RNAase protection analysis, six out of eight wnt genes were expressed in 14 matched cases of normal, adenomatous a nd malignant colorectal tissues. Wnt 2 and wnt 5a were significantly up-reg ulated in the progression from normal through adenoma to carcinoma. Transcr ipts for wnts 4, 7b, 10b and 13, but not wnt 2 and wnt 5a were detected in several colorectal cell lines. in situ hybridization demonstrated that wnt 2 and wnt 5a transcripts were mainly in the lamina propria/stroma region wi th labelling predominantly in macrophages. Immunostaining with CD68 confirm ed the wnt-expressing cells as macrophages. These results show a major diff erence in wnt expression in colon cancer compared to colon adenomas and sug gest stromal wnt expression may play a role in tumour progression. (C) 1999 Cancer Research Campaign.