CD9 overexpression suppressed the liver metastasis and malignant ascites via inhibition of proliferation and motility of small-cell lung cancer cells in NK cell-depleted SCID mice.
CD9, a transmembrane protein known as motility-related protein-1, plays a pivotal role in regulating cell adhesion, motility, and proliferation, and has been regarded as an important metastasis-inhibitory factor of various human cancers. However, little information has been obtained regarding the highly metastatic human small-cell lung cancer (SCLC). In the present study, an SCLC cell line (OS3-R5), lacking CD9 expression, was transfected with human CD9 gene to assess the role of CD9 on the metastatic potential of SCLC. CD9 gene transfection into OS3-R5 cells resulted in cell proliferation and motility in vitro. Parental and mock-transfected OS3-R5 cells developed liver metastasis and malignant ascites when they were intravenously inoculated into NK cell-depleted SCID mice. CD9 gene transfection into OS3-R5 cells caused suppression of the liver metastasis and malignant ascites. Immunohistochemical analysis revealed that the number of proliferating tumor cells was significantly fewer in liver lesions produced by CD9 gene-transfected OS3-R5 cells than those produced by parental or mock control OS3-R5 cells. In addition, no detectable levels of CD9 were expressed in metastatic tumor cells in mice bearing CD9 gene-transfected OS3-R5 cells, as well as those in mice bearing parental or mock control OS3-R5 cells. These results suggest that the restored expression of CD9 in SCLC cells may reduce the metastatic spread of SCLC cells via the inhibition of cell proliferation and motility.
Department of Internal Medicine and Molecular Therapeutics, University of Tokushima Graduate School, Tokushima, Japan.
Rui
R
Zheng
Seiji
S
Yano
Helong
H
Zhang
Emiko
E
Nakataki
Isao
I
Tachibana
Ichiro
I
Kawase
Seiji
S
Hayashi
Saburo
S
Sone
D000818:Animals; D015703:Antigens, CD / Q000096:biosynthesis*; D001201:Ascites / Q000235:genetics / Q000473:pathology*; D018288:Carcinoma, Small Cell / Q000235:genetics / Q000556:secondary*; D002465:Cell Movement; D049109:Cell Proliferation; D006801:Humans; D007150:Immunohistochemistry; D008113:Liver Neoplasms / Q000235:genetics / Q000556:secondary*; D008175:Lung Neoplasms / Q000235:genetics / Q000473:pathology*; D008562:Membrane Glycoproteins / Q000096:biosynthesis*; D051379:Mice; D016513:Mice, SCID; D020133:Reverse Transcriptase Polymerase Chain Reaction; D060245:Tetraspanin 29; D014162:Transfection
D015703:Antigens, CD; C554869:CD9 protein, human; C554870:Cd9 protein, mouse; D008562:Membrane Glycoproteins; D060245:Tetraspanin 29