Identification of a functional role for the protease-activated receptor-1 in hypoxic breast cancer cells

被引：19

作者：

Naldini, Antonella ^{[1
]}

Filippi, Irene ^{[1
]}

Ardinghi, Camilla ^{[1
]}

Silini, Antonietta ^{[2
]}

Giavazzi, Raffaella ^{[2
]}

Carraro, Fabio ^{[1
]}

机构：

[1] Univ Siena, Dept Physiol, I-53100 Siena, Italy

[2] Mario Negri Inst Pharmacol Res, Dept Oncol, I-20157 Milan, Italy

来源：

EUROPEAN JOURNAL OF CANCER | 2009年 / 45卷 / 03期

关键词：

Protease-activated receptor-1; Hypoxia; Tumour microenvironment; Cell survival; Breast cancer; SURVIVAL FACTOR; SOLID TUMORS; T-CELLS; THROMBIN; EXPRESSION; MIGRATION; INVASION; DEATH; PROTEASE-ACTIVATED-RECEPTOR-1; MICROENVIRONMENT;

D O I：

10.1016/j.ejca.2008.10.012

中图分类号：

R73 [肿瘤学];

学科分类号：

100214 ;

摘要：

Aberrant expression of the protease-activated receptor (PAR)-1 has been associated with tumour progression. Indeed, PAR-1 expression correlates with tumour invasiveness, as well as with cancer cell survival. As the tumour microenvironment is characterised by a low oxygen tension, we decided to investigate the role of PAR-1 in cancer cells exposed to a hypoxic microenvironment. in this study we show that hypoxia enhances PAR-1 expression in MDAMB231 breast cancer cells. We next provided evidence for a novel role of PAR-1 in protecting hypoxic breast cancer against cell death, since inhibition of PAR-1 by RNA interference resulted in a decreased cell survival. Finally, we found that treatment of hypoxic MDAMB231 cells with the specific PAR-1 agonist peptide (TRAP) resulted in a significant increase of cell survival and migration. The overall results identify for the first time a functional role for PAR-1 in the cellular responses of breast cancer to a hypoxic microenvironment. (C) 2008 Elsevier Ltd. All rights reserved.

引用

页码：454 / 460

页数：7

共 34 条

[1] CHEMOTACTIC RESPONSE OF MONOCYTES TO THROMBIN [J].