Reduced expression of syndecan-1 affects metastatic potential and clinical outcome in patients with colorectal cancer.
Syndecan-1 is a transmembrane heparansulfate proteoglycan which regulates cell-to-cell or cell-to-extracellular matrix interactions and may influence malignant cell behavior. We investigated the alterations of syndecan-1 expressions in colorectal cancers and analyzed the relationship between histological and clinical characteristics. Syndecan-1 protein expression in colorectal cancer tissues was investigated with immunohistochemical staining of resected specimens. In situ hybridization was performed using syndecan-1 riboprobe to confirm the transcriptional signals. Syndecan-1 mRNA expression in cancer cell lines cultured with or without methylation inhibitor was also analyzed by quantitative PCR. Out of 105 specimens tested, less than 25% of tumor cells were stained with anti-syndecan-1 monoclonal antibody in 36 (34.3%). In situ hybridization showed a similar staining profile to that of immunohistochemistry. Syndecan-1 mRNA expression was increased by the methylation inhibitor 5-aza-2'-deoxycytidine, suggesting that the hypermethylation is involved in the suppression of syndecan-1 expression. Clinically, the incidence of metastasis to lymphnode or liver in patients with syndecan-1-negative tumors was significantly high. Among T1 colorectal cancers displaying a primary invasive phase, lymphnode metastasis, undifferentiated characters and 'budding' of cancer cells were more common in syndecan-1-negative tumors. The survival rate in patients with syndecan-1-negative tumors was decreased significantly in a stage-independent manner. These results suggest that the reduction of syndecan-1 expression in colorectal cancer cells, which is supposed to be regulated at the transcription level, is closely related to invasive character. The evaluation of syndecan-1 expression in colorectal cancer may allow prediction of patients' survival after surgery.
Fujiya
M
M
Third Department of Internal Medicine, Asahikawa Medical College, Asahikawa 078-8510.
Watari
J
J
Ashida
T
T
Honda
M
M
Tanabe
H
H
Fujiki
T
T
Saitoh
Y
Y
Kohgo
Y
Y
D000230:Adenocarcinoma / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism / Q000473:pathology; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001374:Azacitidine / Q000031:analogs & derivatives* / Q000494:pharmacology; D016009:Chi-Square Distribution; D015179:Colorectal Neoplasms / Q000175:diagnosis / Q000235:genetics / Q000378:metabolism* / Q000473:pathology*; D000077209:Decitabine; D005260:Female; D006801:Humans; D007150:Immunohistochemistry; D017403:In Situ Hybridization; D007413:Intestinal Mucosa / Q000737:chemistry / Q000378:metabolism; D008207:Lymphatic Metastasis; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D008745:Methylation / Q000187:drug effects; D008875:Middle Aged; D009362:Neoplasm Metastasis; D009367:Neoplasm Staging; D011379:Prognosis; D011509:Proteoglycans / Q000032:analysis / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D012334:RNA, Neoplasm / Q000235:genetics / Q000378:metabolism; D016019:Survival Analysis; D053668:Syndecan-1; D053667:Syndecans; D014407:Tumor Cells, Cultured
D008562:Membrane Glycoproteins; D011509:Proteoglycans; D012333:RNA, Messenger; D012334:RNA, Neoplasm; C508241:SDC1 protein, human; D053668:Syndecan-1; D053667:Syndecans; D000077209:Decitabine; D001374:Azacitidine