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BMC Cancer. 2017 Dec 20;17(1):875. doi: 10.1186/s12885-017-3894-0.

Isoprenaline/β2-AR activates Plexin-A1/VEGFR2 signals via VEGF secretion in gastric cancer cells to promote tumor angiogenesis.

Author information

1
Department of Pathology; Cancer Research Laboratory, Chengde Medical College, Shangerdaohezi Avenue, Chengde, Hebei, 067000, People's Republic of China.
2
Institute of Basic Medical Sciences, Chengde Medical College, Chengde, 067000, People's Republic of China.
3
Department of Pharmacology, Chengde Medical College, Chengde, 067000, People's Republic of China.
4
Department of Pathogenic Microorganism, Chengde Medical College, Chengde, 067000, People's Republic of China.
5
Department of Pathology, Chengde Medical College, Chengde, 067000, People's Republic of China.
6
Department of General Surgery, the 266th Hospital of Chinese People's Liberation Army, Puning Avenue, Chengde, Hebei, 067000, People's Republic of China.
7
Department of General Surgery, the 266th Hospital of Chinese People's Liberation Army, Puning Avenue, Chengde, Hebei, 067000, People's Republic of China. luyanjiehappy@163.com.
8
Department of Pathology; Cancer Research Laboratory, Chengde Medical College, Shangerdaohezi Avenue, Chengde, Hebei, 067000, People's Republic of China. youngcheer2003@foxmail.com.

Abstract

BACKGROUND:

The role of stress signals in regulating gastric cancer initiation and progression is not quite clear. It is known that stress signals modulate multiple processes such as immune function, cell migration and angiogenesis. However, few studies have investigated the mechanisms of how stress signals contribute to gastric cancer angiogenesis.

METHODS:

Here, we used β2-adrenergic receptor (β2-AR) agonist isoprenaline to imitate a stress signal and demonstrated the molecular mechanism underlying stress's influence on tumor angiogenesis.

RESULTS:

We found that isoprenaline stimulated vascular endothelial growth factor (VEGF) secretion in gastric cancer cells and plexin-A1 expression was induced by human recombinant VEGF165 in both gastric cancer cells and vascular endothelial cells. Furthermore, interfere with plexin-A1 expression in gastric cancer cells influence HUVEC tube formation, migration and tumor growth in vivo.

CONCLUSIONS:

These findings suggest that isoprenaline stimulate VGEF secretion and subsequently up-regulate the expression of plexin-A1 and VEGFR2 in gastric cancer cells, which form a positive impetus to promote tumor angiogenesis. This study reveals a novel molecular mechanism that a stress signal like isoprenaline may enhance angiogenesis via activating plexin-A1/VEGFR2 signaling pathway in gastric cancer, which may be a potential target in development of an anti-angiogenic therapy for gastric cancer.

KEYWORDS:

Angiogenesis; Gastric cancer; Isoprenaline; Plexin-A1; VEGFR2

PMID:
29262812
PMCID:
PMC5738852
DOI:
10.1186/s12885-017-3894-0
[Indexed for MEDLINE]
Free PMC Article

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