Down-regulation of layilin, a novel hyaluronan receptor, via RNA interference, inhibits invasion and lymphatic metastasis of human lung A549 cells

被引:25
作者
Chen, Zhengtang [1 ]
Zhuo, Wenlei [1 ]
Wang, Yan [2 ]
Ao, Xujun [1 ]
An, Jianghong [1 ]
机构
[1] Third Mil Med Univ, Xinqiao Hosp, Inst Canc, Chongqing 400037, Peoples R China
[2] Third Mil Med Univ, Xinqiao Hosp, Inst Resp Dis, Chongqing 400037, Peoples R China
关键词
A549 human lung cells; hyaluronan (HYA) receptor; layilin; lung carcinoma; lymphatic invasion and metastasis; RNA interference (RNAi); gene therapy;
D O I
10.1042/BA20070138
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 [生物化学与分子生物学]; 081704 [应用化学];
摘要
Human lung carcinoma is a highly metastatic tumour that leads to a high death rate and in which lymphatic metastasis is an important early event. HYA (hyaluronan) is involved in the invasion of a variety of tumour cells. Layilin, a specific and novel HYA receptor, was detected in the human lung cell line A549 in our preliminary research, and was hypothesized to play an essential role in cell motility and tumour lymphatic metastasis. In the present study we found that, as expected, suppression of layilin expression by RNA interference significantly inhibited A549-cell invasion and migration in vitro and lymphatic metastasis in vivo and thereby resulted in the increased survival of tumour bearing mice. These findings suggested that layilin might play crucial roles in lymphatic metastasis of lung carcinoma and that suppression of layilin expression might be a promising strategy for treatment of human lung carcinoma.
引用
收藏
页码:89 / 96
页数:8
相关论文
共 32 条
[1]
ICAM-1 mediated peritoneal carcinomatosis, a target for therapeutic intervention [J].
Alkhamesi, NA ;
Ziprin, P ;
Pfistermuller, K ;
Peck, DH ;
Darzi, AW .
CLINICAL & EXPERIMENTAL METASTASIS, 2005, 22 (06) :449-459
[2]
Sphingosine 1-phosphate inhibits cell migration in C2C12 myoblasts [J].
Becciolini, L ;
Meacci, E ;
Donati, C ;
Cencetti, F ;
Rapizzi, E ;
Bruni, P .
BIOCHIMICA ET BIOPHYSICA ACTA-MOLECULAR AND CELL BIOLOGY OF LIPIDS, 2006, 1761 (01) :43-51
[3]
Layilin, a cell surface hyaluronan receptor, interacts with merlin and radixin [J].
Bono, P ;
Cordero, E ;
Johnson, K ;
Borowsky, M ;
Ramesh, V ;
Jacks, T ;
Hynes, RO .
EXPERIMENTAL CELL RESEARCH, 2005, 308 (01) :177-187
[4]
Layilin, a novel integral membrane protein, is a hyaluronan receptor [J].
Bono, P ;
Rubin, K ;
Higgins, JMG ;
Hynes, RO .
MOLECULAR BIOLOGY OF THE CELL, 2001, 12 (04) :891-900
[5]
Layilin, a novel talin-binding transmembrane protein homologous with C-type lectins, is localized in membrane ruffles [J].
Borowsky, ML ;
Hynes, RO .
JOURNAL OF CELL BIOLOGY, 1998, 143 (02) :429-442
[6]
Cantor Jerome O., 2006, Inflammation & Allergy Drug Targets, V5, P257, DOI 10.2174/187152806779010936
[7]
Down-regulation of vascular endothelial cell growth factor-C expression using small interfering RNA vectors in mammary tumors inhibits tumor lymphangiogenesis and spontaneous metastasis and enhances survival [J].
Chen, ZT ;
Varney, ML ;
Backora, MW ;
Cowan, K ;
Solheim, JC ;
Talmadge, JE ;
Singh, RK .
CANCER RESEARCH, 2005, 65 (19) :9004-9011
[8]
A role for hyaluronan in the preservation of interstitial structure [J].
Coleman, PJ .
MICROCIRCULATION, 2005, 12 (02) :209-221
[9]
Hyaluronan promotes tumor lymphangiogenesis and intralymphantic tumor growth in xenografts [J].
Guo, LX ;
Zou, K ;
Ju, JH ;
Xie, H .
ACTA BIOCHIMICA ET BIOPHYSICA SINICA, 2005, 37 (09) :601-606
[10]
Quantitative and comparative studies of the vocal fold extracellular matrix - I: Elastic fibers and hyaluronic acid [J].
Hahn, MS ;
Kobler, JB ;
Starcher, BC ;
Zeitels, SM ;
Langer, R .
ANNALS OF OTOLOGY RHINOLOGY AND LARYNGOLOGY, 2006, 115 (02) :156-164