Involvement of p38α mitogen-activated protein kinase in lung metastasis of tumor cells

被引:32
作者
Matsuo, Yuji
Amano, Shinya
Furuya, Mitsuko
Namiki, Kana
Sakurai, Kanako
Nishiyama, Mariko
Sudo, Tatsuhiko
Tatsumi, Koichiro
Kuriyama, Takayuki
Kimura, Sadao
Kasuya, Yoshitoshi
机构
[1] Chiba Univ, Grad Sch Med, Dept Biochem & Mol Pharmacol, Chuo Ku, Chiba 2608670, Japan
[2] Chiba Univ, Grad Sch Med, Dept Respirol, Chuo Ku, Chiba 2608670, Japan
[3] Chiba Univ, Grad Sch Med, Dept Mol Pathol, Chuo Ku, Chiba 2608670, Japan
[4] RIKEN, Antibiot Lab & Bioarchitect Res Grp, Wako, Saitama 3510198, Japan
关键词
D O I
10.1074/jbc.M604371200
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
To study the role of p38 mitogen-activated protein kinase ( p38) activity during the process of metastasis, p38 alpha(+/-) mice were subjected to an in vivo metastasis assay. The number of lung colonies of tumor cells intravenously injected in p38 alpha(-/-) mice was markedly decreased compared with that in wild-type (WT) mice. On the other hand, the time-dependent increase in tumor volume after subcutaneous tumor cells transplantation was comparable between WT and p38 alpha(+/-) mice. Platelets of p38 alpha(+/-) mice were poorly bound to tumor cells in vitro and in vivo compared with those of WT mice. E- and P-selectin mRNAs were markedly induced in the lung after intravenous injection of tumor cells. However, the induction of these selectin mRNAs in p38 alpha(+/-) mice was weaker than that in WT mice. Furthermore, the resting expression levels of E-selectin in lung endothelial cells and P-selectin in platelets of p38 alpha(+/-) mice were suppressed compared with those of WT mice. The number of tumor cells attached on lung endothelial cells of p38 alpha(+/-) mice was significantly reduced compared with that of WT mice. The transmigrating activity of tumor cells through lung endothelial cells of p38 alpha(+/-) mice was similar to that of WT mice. These results suggest that p38 alpha plays an important role in extravasation of tumor cells, possibly through regulating the formation of tumor-platelet aggregates and their interaction with the endothelium involved in a step of hematogenous metastasis.
引用
收藏
页码:36767 / 36775
页数:9
相关论文
共 45 条
[1]   Essential role of p38α MAP kinase in placental but not embryonic cardiovascular development [J].
Adams, RH ;
Porras, A ;
Alonso, G ;
Jones, M ;
Vintersten, K ;
Panelli, S ;
Valladares, A ;
Perez, L ;
Klein, R ;
Nebreda, AR .
MOLECULAR CELL, 2000, 6 (01) :109-116
[2]   Green fluorescent protein tagging of extracellular signal-regulated kinase and p38 pathways reveals novel dynamics of pathway activation during primary and metastatic growth [J].
Aguirre-Ghiso, JA ;
Ossowski, L ;
Rosenbaum, SK .
CANCER RESEARCH, 2004, 64 (20) :7336-7345
[3]   Redirection of tumor metastasis by expression of E-selectin in vivo [J].
Biancone, L ;
Araki, M ;
Araki, K ;
Vassalli, P ;
Stamenkovic, I .
JOURNAL OF EXPERIMENTAL MEDICINE, 1996, 183 (02) :581-587
[4]   Heparin and cancer revisited: Mechanistic connections involving platelets, P-selectin, carcinoma mucins, and tumor metastasis [J].
Borsig, L ;
Wong, R ;
Feramisco, J ;
Nadeau, DR ;
Varki, NM ;
Varki, A .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2001, 98 (06) :3352-3357
[5]   Mechanism of p38 MAP kinase activation in vivo [J].
Brancho, D ;
Tanaka, N ;
Jaeschke, A ;
Ventura, JJ ;
Kelkar, N ;
Tanaka, Y ;
Kyuuma, M ;
Takeshita, T ;
Flavell, RA ;
Davis, RJ .
GENES & DEVELOPMENT, 2003, 17 (16) :1969-1978
[6]   PARALLEL SIGNAL-PROCESSING AMONG MAMMALIAN MAPKS [J].
CANO, E ;
MAHADEVAN, LC .
TRENDS IN BIOCHEMICAL SCIENCES, 1995, 20 (03) :117-122
[7]  
Hale KK, 1999, J IMMUNOL, V162, P4246
[8]   Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation [J].
Han, J ;
Jiang, Y ;
Li, Z ;
Kravchenko, VV ;
Ulevitch, RJ .
NATURE, 1997, 386 (6622) :296-299
[9]   The p38 kinases MKK4 and MKK6 suppress metastatic colonization in human ovarian carcinoma [J].
Hickson, JA ;
Huo, DZ ;
Vander Griend, DJ ;
Lin, AN ;
Rinker-Schaeffer, CW ;
Yamada, SD .
CANCER RESEARCH, 2006, 66 (04) :2264-2270
[10]   Urokinase plasminogen activator/urokinase-specific surface receptor expression and matrix invasion by breast cancer cells requires constitutive p38α mitogen-activated protein kinase activity [J].
Huang, S ;
New, L ;
Pan, ZX ;
Han, JH ;
Nemerow, GR .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2000, 275 (16) :12266-12272