Increased migration and metastatic potential of tumor cells expressing aquaporin water channels

被引:270
作者
Hu, Jie
Verkman, A. S.
机构
[1] Univ Calif San Francisco, Dept Med, San Francisco, CA 94143 USA
[2] Univ Calif San Francisco, Dept Physiol, Cardiovasc Res Inst, San Francisco, CA 94143 USA
关键词
aquaporin; water channel; tumor metastasis; cell migration; cancer;
D O I
10.1096/fj.06-5930fje
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
Aquaporin (AQP) water channels are expressed in high-grade tumor cells of different tissue origins. Based on the involvement of AQPs in angiogenesis and cell migration, we tested whether AQP expression in tumor cells might enhance their migration and metastatic potential. Transfection of B16F10 and 4T1 tumor cells with AQP1 did not affect their appearance, size, growth, or substrate adherence but increased their plasma membrane osmotic water permeability by 5- to 10-fold. In vitro analysis of cell migration by transwell assay, wound healing and video microscopy showed a 2- to 3-fold accelerated migration of the AQP1-expressing tumor cells compared to control cells. In mice, AQP1 expression increased tumor cell extravasation by > 1.5-fold as quantified by counting tumor cells in lung at 6 h after tail vein injection of a mixture of fluorescently tagged AQP1-expressing and control tumor cells. AQP1 expression also increased by 3-fold the number of lung metastases 14 days after tail vein injection of tumor cells, with alveolar wall infiltration seen with AQP1-expressing tumor cells. Our results provide evidence for AQP-facilitated tumor cell migration and spread, suggesting a novel function for AQP expression in high-grade tumors. AQP inhibition may thus reduce the metastatic potential of some tumors.
引用
收藏
页码:1892 / +
页数:9
相关论文
共 32 条
[1]   Aquaporin water channels - from atomic structure to clinical medicine [J].
Agre, P ;
King, LS ;
Yasui, M ;
Guggino, WB ;
Ottersen, OP ;
Fujiyoshi, Y ;
Engel, A ;
Nielsen, S .
JOURNAL OF PHYSIOLOGY-LONDON, 2002, 542 (01) :3-16
[2]   Identification of astrocytoma associated genes including cell surface markers [J].
Boon, K ;
Edwards, JB ;
Eberhart, CG ;
Riggins, GJ .
BMC CANCER, 2004, 4 (1)
[3]   Water channel (aquaporin 1) expression and distribution in mammary carcinomas and glioblastomas [J].
Endo, M ;
Jain, RK ;
Witwer, B ;
Brown, D .
MICROVASCULAR RESEARCH, 1999, 58 (02) :89-98
[4]   BIOLOGICAL DIVERSITY IN METASTATIC NEOPLASMS - ORIGINS AND IMPLICATIONS [J].
FIDLER, IJ ;
HART, IR .
SCIENCE, 1982, 217 (4564) :998-1003
[5]   Tumour-cell invasion and migration: Diversity and escape mechanisms [J].
Friedl, P ;
Wolf, K .
NATURE REVIEWS CANCER, 2003, 3 (05) :362-374
[6]   Glycerol replacement corrects defective skin hydration, elasticity, and barrier function in aquaporin-3-deficient mice [J].
Hara, M ;
Verkman, AS .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2003, 100 (12) :7360-7365
[7]   Progressive adipocyte hypertrophy in aquaporin-7-deficient mice - Adipocyte glycerol permeability as a novel regulator of fat accumulation [J].
Hara-Chikuma, M ;
Sohara, E ;
Rai, T ;
Ikawa, M ;
Okabe, M ;
Sasaki, S ;
Uchida, S ;
Verkman, AS .
JOURNAL OF BIOLOGICAL CHEMISTRY, 2005, 280 (16) :15493-15496
[8]   Aquaporin-1 facilitates epithelial cell migration in kidney proximal tubule [J].
Hara-Chikuma, Mariko ;
Verkman, A. S. .
JOURNAL OF THE AMERICAN SOCIETY OF NEPHROLOGY, 2006, 17 (01) :39-45
[9]   Collecting duct carcinoma:: an entity to be redefined? [J].
Kafé, H ;
Verbavatz, JM ;
Cochand-Priollet, B ;
Castagnet, P ;
Vieillefond, A .
VIRCHOWS ARCHIV, 2004, 445 (06) :637-640
[10]   Cell migration: A physically integrated molecular process [J].
Lauffenburger, DA ;
Horwitz, AF .
CELL, 1996, 84 (03) :359-369