Transduction of KAI1/CD82 cDNA promotes hematogenous spread of human lung-cancer cells in natural killer cell-depleted SCID mice.
KAI1, which is identical to CD82, was initially identified as a metastasis-suppressor gene for human prostate cancer, and its expression is reported to be a favorable prognostic factor for operable human lung cancer. In this study, we examined the functional role of KAI1/CD82 in the late phase of metastatic spread of human lung-cancer cells. For this, KAI1/CD82 cDNA was introduced into KAI1/CD82 low-expressing human lung-cancer cell lines, SBC-3 and PC-14, and then the metastatic potential of the transformants was analyzed by i.v. inoculation of KAI1/CD82-transduced cells, SBC-3/KAI1 and PC-14/KAI1, into NK cell-depleted SCID mice. Contrary to our expectations, KAI1/CD82 gene transfer promoted multiorgan metastasis of i.v.-inoculated human lung-cancer cells, while s.c. tumor growth was unaffected. Cancer cells from metastatic tumors of NK cell-depleted SCID mice injected i.v. with SBC-3/KAI1 expressed appreciable cell-surface KAI1/CD82, and cells not expressing KAI1/CD82 (revertants) were not detected in the tumors. Our findings indicate that under conditions where the host's natural cytotoxicity is suppressed, KAI1/CD82 may enhance the formation of tumors by circulating lung-cancer cells at metastatic sites.
Shinohara
T
T
Third Department of Internal Medicine, University of Tokushima School of Medicine, 3-18-15 Kuramoto-cho, Tokushima 770, Japan. shinoben@clin.med.tokushima-u.ac.jp
Nishimura
N
N
Hanibuchi
M
M
Nokihara
H
H
Miki
T
T
Hamada
H
H
Sone
S
S
D000818:Animals; D015703:Antigens, CD; D002448:Cell Adhesion; D002460:Cell Line; D003602:Cytotoxicity, Immunologic; D004730:Endothelium, Vascular / Q000166:cytology; D051861:Kangai-1 Protein; D007694:Killer Cells, Natural / Q000502:physiology*; D008175:Lung Neoplasms / Q000473:pathology*; D008297:Male; D008562:Membrane Glycoproteins / Q000032:analysis / Q000235:genetics / Q000502:physiology*; D051379:Mice; D016513:Mice, SCID; D009360:Neoplastic Cells, Circulating; D011518:Proto-Oncogene Proteins; D014161:Transduction, Genetic
D015703:Antigens, CD; C497689:Cd82 antigen, mouse; D051861:Kangai-1 Protein; D008562:Membrane Glycoproteins; D011518:Proto-Oncogene Proteins