An agarose spot chemotaxis assay for chemokine receptor antagonists

被引：18

作者：

Vinader, Victoria ^{[1
]}

Al-Saraireh, Yousef ^{[1
]}

Wiggins, Helen L. ^{[2
]}

Rappoport, Joshua Z. ^{[2
]}

Shnyder, Steve D. ^{[1
]}

Patterson, Laurence H. ^{[1
]}

Afarinkia, Kamyar ^{[1
]}

机构：

[1] Univ Bradford, Inst Canc Therapeut, Bradford BD7 1DP, W Yorkshire, England

[2] Univ Birmingham, Sch Biosci, Birmingham B15 2TT, W Midlands, England

来源：

JOURNAL OF PHARMACOLOGICAL AND TOXICOLOGICAL METHODS | 2011年 / 64卷 / 03期

关键词：

Chemotaxis; Assay; CXCR4; Antagonist; AMD3100; ICT5040; CXCR4; AMD3100; MIGRATION; CANCER; CELLS; INHIBITION; INVASION;

D O I：

10.1016/j.vascn.2011.01.004

中图分类号：

R9 [药学];

学科分类号：

1007 ;

摘要：

Introduction: Chemokines are important players in directing the migration of cancer cells as part of the metastatic process. The aim of this study is to develop an easy-to-perform, reliable, and inexpensive assay for rapid analysis of anti-chemotactic activity of chemokine antagonists under a number of experimental conditions. Methods: An agarose spot containing the chemokine chemoattractant is applied to a glass petri dish. Live cells in a media, both with and without a chemokine antagonist, are added to the dish and, following cell adhesion, the migration under the agarose spot is observed and analysed by microscopy. Results: In the absence of CXCL12 in the agarose, no migration under the agarose spot is detected. In the presence of CXCL12, significant migration under the agarose spot is observed which can be retarded if a neutralising monoclonal antibody or a small molecule antagonist is added to the media. Discussion: This experimental configuration is a reliable, inexpensive and easy-to-perform chemotaxis assay, which enables assessment of the activity of CXCR4 antagonists. (C) 2011 Elsevier Inc. All rights reserved.

引用

页码：213 / 216

页数：4

共 22 条

[1] Stromal cell-derived factor-1α plays a critical role in stem cell recruitment to the heart after myocardial infarction but is not sufficient to induce homing in the absence of injury [J].

Abbott, JD ;

Huang, Y ;

Liu, D ;

Hickey, R ;

Krause, DS ;

Giordano, FJ .

CIRCULATION, 2004, 110 (21) :3300-3305

[2] The significance of cancer cell expression of the chemokine receptor CXCR4 [J].

Balkwill, F .

SEMINARS IN CANCER BIOLOGY, 2004, 14 (03) :171-179

[3] Cancer and the chemokine network [J].

Balkwill, F .

NATURE REVIEWS CANCER, 2004, 4 (07) :540-550

[4] Chemokine biology in cancer [J].

Balkwill, F .

SEMINARS IN IMMUNOLOGY, 2003, 15 (01) :49-55

[5] The chemokine stromal cell-derived factor-1 regulates the migration of sensory neuron progenitors [J].

Belmadani, A ;

Tran, PB ;

Ren, DJ ;

Assimacopoulos, S ;

Grove, EA ;

Miller, RJ .

JOURNAL OF NEUROSCIENCE, 2005, 25 (16) :3995-4003

[6] CXCR4: a key receptor in the crosstalk between tumor cells and their microenvironment [J].

Burger, JA ;

Kipps, TJ .

BLOOD, 2006, 107 (05) :1761-1767

[7] Potential clinical applications of the CXCR4 antagonist bicyclam AMD3100 [J].

De Clercq, E .

MINI-REVIEWS IN MEDICINAL CHEMISTRY, 2005, 5 (09) :805-824

[8] The bicyclam AMD3 100 story [J].

De Clercq, E .

NATURE REVIEWS DRUG DISCOVERY, 2003, 2 (07) :581-587

[9] Characterization of the molecular pharmacology of AMD3100: A specific antagonist of the G-protein coupled chemokine receptor, CXCR4 [J].

Fricker, Simon P. ;

Anastassov, Virginia ;

Cox, Jennifer ;

Darkes, Marilyn C. ;

Grujic, Ognjen ;

Idzan, Stefan R. ;

Labrecque, Jean ;

Lau, Gloria ;

Mosi, Renee M. ;

Nelson, Kim L. ;

Qin, Ling ;

Santucci, Zeffy ;

Wong, Rebecca S. Y. .

BIOCHEMICAL PHARMACOLOGY, 2006, 72 (05) :588-596

[10] Chemokine receptor inhibition by AMD3100 is strictly confined to CXCR4 [J].

Hatse, S ;

Princen, K ;

Bridger, G ;

De Clercq, E ;

Schols, D .

FEBS LETTERS, 2002, 527 (1-3) :255-262

← 1 2 3 →