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 investigated whether aberrant regulation of upstream ligands stimulating this pathway occur in colon cancer. Using RNAase protection analysis, six out of eight wnt genes were expressed in 14 matched cases of normal, adenomatous and malignant colorectal tissues. Wnt 2 and wnt 5a were significantly up-regulated in the progression from normal through adenoma to carcinoma. Transcripts 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 with labelling predominantly in macrophages. Immunostaining with CD68 confirmed the wnt-expressing cells as macrophages. These results show a major difference in wnt expression in colon cancer compared to colon adenomas and suggest stromal wnt expression may play a role in tumour progression.
Smith
K
K
ICRF Molecular Oncology Laboratory, John Radcliffe Hospital, Oxford, UK.
Bui
T D
TD
Poulsom
R
R
Kaklamanis
L
L
Williams
G
G
Harris
A L
AL
D000230:Adenocarcinoma / Q000235:genetics* / Q000473:pathology; D000236:Adenoma / Q000235:genetics* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D003110:Colonic Neoplasms / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D003111:Colonic Polyps / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D018076:DNA, Complementary / Q000235:genetics; D018450:Disease Progression; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D017403:In Situ Hybridization; D008264:Macrophages / Q000378:metabolism*; D008875:Middle Aged; D005810:Multigene Family; D009363:Neoplasm Proteins / Q000096:biosynthesis* / Q000235:genetics; D020033:Protein Isoforms / Q000096:biosynthesis* / Q000235:genetics; D011518:Proto-Oncogene Proteins / Q000096:biosynthesis* / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis; D012334:RNA, Neoplasm / Q000096:biosynthesis; D014407:Tumor Cells, Cultured; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051154:Wnt2 Protein; D029961:Zebrafish Proteins
D018076:DNA, Complementary; D009363:Neoplasm Proteins; D020033:Protein Isoforms; D011518:Proto-Oncogene Proteins; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C495244:WNT2 protein, human; C085389:WNT5A protein, human; D051153:Wnt Proteins; D000071818:Wnt-5a Protein; D051154:Wnt2 Protein; D029961:Zebrafish Proteins