Tumor-associated antigen L6 and the invasion of human lung cancer cells.
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.
Kao
Yu-Rong
YR
Institute of Biomedical Sciences, Academia Sinica, Taipei, Taiwan 115, Republic of China.
Shih
Jin-Yuan
JY
Wen
Wei-Chun
WC
Ko
Ya-Ping
YP
Chen
Bing-Mae
BM
Chan
Yi-Lin
YL
Chu
Yi-Wen
YW
Yang
Pan-Chyr
PC
Wu
Cheng-Wen
CW
Roffler
Steve R
SR
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
D000911:Antibodies, Monoclonal; D000951:Antigens, Neoplasm; D000954:Antigens, Surface; D009363:Neoplasm Proteins; D012333:RNA, Messenger; C074075:TM4SF1 protein, human; D003094:Collagen