Novel spliced form of a lens protein as a novel lung cancer antigen, Lengsin splicing variant 4.
A glutamine synthetase I family protein, Lengsin, was previously identified as a novel lens-specific transcript in the vertebrate eye. In this report, we show for the first time that Lengsin is a novel tumor-associated antigen expressed ectopically in lung cancer. Interestingly, a novel spliced form of human Lengsin termed 'splicing variant 4', gaining exon 3 that codes extra 63 amino acids, is the dominant transcript form in lung cancer cells. Lengsin mRNA could be detected in 7 of 12 (58%) lung cancer cell lines and 7 of 7 (100%) surgically resected lung cancer tissues. On the other hand, Lengsin transcripts could not be detected in normal major tissues or in other cancer cell lines, including melanoma, colorectal carcinoma, breast carcinoma and hepatocellular carcinoma. In addition, knockdown of Lengsin mRNA with RNAi caused cell death and a decrease of cell viability, suggesting that Lengsin has some essential role in cell survival. Since the lens is an immune-privileged site, we regard Lengsin as a highly immunogenic cancer antigen. Anti-Lengsin autoantibodies were detectable in sera of lung cancer patients, although these patients did not show any lens-related disturbances. Hence, Lengsin splicing variant 4 might be an immunogenic lung cancer-specific antigen that is suitable as a diagnostic marker and for molecular targeting therapy, including immunotherapy.
Nakatsugawa
Munehide
M
Department of Pathology, Sapporo Medical University School of Medicine, Chuo-ku, Sapporo, Japan.
Hirohashi
Yoshihiko
Y
Torigoe
Toshihiko
T
Asanuma
Hiroko
H
Takahashi
Akari
A
Inoda
Satoko
S
Kiriyama
Kenji
K
Nakazawa
Emiri
E
Harada
Kenji
K
Takasu
Hideo
H
Tamura
Yasuaki
Y
Kamiguchi
Kenjiro
K
Shijubo
Noriharu
N
Honda
Ryoichi
R
Nomura
Naohiro
N
Hasegawa
Tadashi
T
Takahashi
Hiroki
H
Sato
Noriyuki
N
D000230:Adenocarcinoma / Q000235:genetics / Q000276:immunology; D000368:Aged; D000951:Antigens, Neoplasm; D018287:Carcinoma, Large Cell / Q000235:genetics / Q000276:immunology; D002294:Carcinoma, Squamous Cell / Q000235:genetics / Q000276:immunology; D016022:Case-Control Studies; D045744:Cell Line, Tumor; D005136:Eye Proteins / Q000235:genetics* / Q000378:metabolism; D005260:Female; D005974:Glutamate-Ammonia Ligase / Q000235:genetics* / Q000276:immunology; D006801:Humans; D007150:Immunohistochemistry; D007908:Lens, Crystalline / Q000378:metabolism*; D008175:Lung Neoplasms / Q000235:genetics / Q000276:immunology* / Q000473:pathology; D008297:Male; D008875:Middle Aged; D020033:Protein Isoforms / Q000276:immunology*; D019154:Protein Splicing; D012333:RNA, Messenger / Q000378:metabolism; D034741:RNA, Small Interfering / Q000378:metabolism; D055752:Small Cell Lung Carcinoma / Q000235:genetics / Q000276:immunology; D014162:Transfection
D000951:Antigens, Neoplasm; D005136:Eye Proteins; D020033:Protein Isoforms; D012333:RNA, Messenger; D034741:RNA, Small Interfering; D005974:Glutamate-Ammonia Ligase; C507977:LGSN protein, human