title: Tumor-associated antigen L6 and the invasion of human lung cancer cells.
abstract: Metastasis is a coordinated process that depends on the interaction of cancer cells with the tumor microenvironment. Members of the transmembrane-4 superfamily (TM4SF) of surface proteins have been implicated in the regulation of cancer cell metastasis, and the expression of several TM4SF members on tumor cells is inversely correlated with patient prognosis. The tumor-associated antigen L6 (TAL6), a distant member of the TM4SF, is expressed on most epithelial cell carcinomas and is a target for antibody-mediated therapy. We examined whether TAL6 may play a role in cancer metastasis by using an established series of human lung carcinoma cell lines (CL1-0 to CL1-5) that exhibit increasing invasiveness in vitro and in vivo. We found that TAL6 expression correlated with the in vitro invasiveness of CL lung carcinoma cells (r(2) = 0.98) and human carcinoma cells (r(2) = 0.69). Forced expression of TAL6 on CL1-0 lung carcinoma cells significantly increased their in vitro invasiveness and decreased the survival of SCID mice in an experimental metastasis model. Specific antibody against TAL6 (monoclonal antibody L6) significantly reduced the migration and invasiveness of CL1-5 lung carcinoma cells. The effects of monoclonal antibody L6 on CL1-5 invasion required clustering of TAL6 on the cell surface. Real-time reverse transcription-PCR of lung cancer specimens showed that increased expression of TAL6 was significantly associated with early postoperative relapse (P = 0.034) and shorter survival (P = 0.025) in squamous cell lung cancer patients. Thus, TAL6 appears to be involved in cancer invasion and metastasis.
authors.affiliation: Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan 115, Republic of China.
authors.forename: Yu-Rong
authors.initials: YR
authors.lastname: Kao
authors.forename: Jin-Yuan
authors.initials: JY
authors.lastname: Shih
authors.forename: Wei-Chun
authors.initials: WC
authors.lastname: Wen
authors.forename: Ya-Ping
authors.initials: YP
authors.lastname: Ko
authors.forename: Bing-Mae
authors.initials: BM
authors.lastname: Chen
authors.forename: Yi-Lin
authors.initials: YL
authors.lastname: Chan
authors.forename: Yi-Wen
authors.initials: YW
authors.lastname: Chu
authors.forename: Pan-Chyr
authors.initials: PC
authors.lastname: Yang
authors.forename: Cheng-Wen
authors.initials: CW
authors.lastname: Wu
authors.forename: Steve R
authors.initials: SR
authors.lastname: Roffler
mesh_terms: D000368:Aged; D000818:Animals; D000911:Antibodies, Monoclonal / Q000737:chemistry; D000951:Antigens, Neoplasm / Q000096:biosynthesis*; D000954:Antigens, Surface / Q000096:biosynthesis; D002294:Carcinoma, Squamous Cell / Q000378:metabolism / Q000401:mortality; D002448:Cell Adhesion; D045744:Cell Line, Tumor; D002465:Cell Movement; D003094:Collagen / Q000378:metabolism; D018572:Disease-Free Survival; D004305:Dose-Response Relationship, Drug; D005260:Female; D006801:Humans; D008175:Lung Neoplasms / Q000378:metabolism* / Q000401:mortality / Q000473:pathology*; D008297:Male; D051379:Mice; D016513:Mice, SCID; D008875:Middle Aged; D009361:Neoplasm Invasiveness; D009362:Neoplasm Metastasis; D009363:Neoplasm Proteins / Q000096:biosynthesis; D012333:RNA, Messenger / Q000378:metabolism; D012008:Recurrence; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014162:Transfection
chemical_list: D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C074075:TM4SF1 protein, human; D003094:Collagen