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.
Zheng
Rui
R
Department of Internal Medicine and Molecular Therapeutics, University of Tokushima Graduate School, Tokushima, Japan.
Yano
Seiji
S
Zhang
Helong
H
Nakataki
Emiko
E
Tachibana
Isao
I
Kawase
Ichiro
I
Hayashi
Seiji
S
Sone
Saburo
S
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