[Cellular and molecular biological study of the laminin-binding protein and its clinical application].
Tumor invasion and metastasis involve the interaction between tumor cells and basement membrane, which is mediated in part by laminin receptors. To search for tumor-associated-genes which can be used as new markers in colon cancers with known poor prognosis, cDNA libraries from a colon cancer cell line and colonic tissues were constructed and screened. We selected a cDNA clone which encodes 32-kD laminin-binding protein (LBP-32), and showed increased mRNA expression of LBP-32 in colon carcinoma. This mRNA expression was also correlated with clinical tumor staging. Furthermore, to investigate the role of LBP-32 in cancer invasion and metastasis, cell adhesion assays and in vitro invasion assays were performed, using anti-sense RNA of LBP-32 to block the synthesis of LBP-32. Results showed that anti-sense RNA of LBP-32 inhibits tumor cell attachment and invasiveness in vitro in transfectants of a colon cancer cell line. These data suggest that LBP-32 may play an important role in colon cancer progression, and that LBP-32 may be used as a marker of biological aggressiveness. These findings also imply that laminin receptors may provide a target for novel therapeutic strategies: modulating LBP-32 expression by anti-sense RNA or monoclonal antibodies may have clinical application in colorectal cancer therapy.
Mafune
K
K
Second Department of Surgery, Faculty of Medicine, University of Tokyo, Japan.
Konishi
T
T
Idezuki
Y
Y
Steele
G D
GD
Ravikumar
T S
TS
D000230:Adenocarcinoma / Q000235:genetics / Q000473:pathology; D014408:Biomarkers, Tumor; D003110:Colonic Neoplasms / Q000235:genetics / Q000473:pathology; D005260:Female; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008297:Male; D009361:Neoplasm Invasiveness; D009857:Oncogenes / Q000235:genetics; D012333:RNA, Messenger / Q000235:genetics; D017474:Receptors, Laminin / Q000235:genetics*
D014408:Biomarkers, Tumor; D012333:RNA, Messenger; D017474:Receptors, Laminin