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Oncotarget. 2015 Apr 30;6(12):10016-29.

Stat3 orchestrates interaction between endothelial and tumor cells and inhibition of Stat3 suppresses brain metastasis of breast cancer cells.

Author information

1
Department of Neurosurgery, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
2
Institute of Anatomy and Cell Biology, National Yang-Ming University, Taipei, Taiwan.
3
Department of Neuro-Oncology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
4
Department of Pathology, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
5
Department of Experimental Therapeutics, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
6
Division of Cardiology and McAllister Heart Institute, University of North Carolina, Chapel Hill, North Carolina, USA.
7
Gastroenterology, Hepatology & Nutrition, The University of Texas MD Anderson Cancer Center, Houston, Texas, USA.
8
Program in Cancer Biology, The University of Texas Graduate School of Biomedical Sciences at Houston, Houston, Texas, USA.

Abstract

Brain metastasis is a major cause of morbidity and mortality in patients with breast cancer. Our previous studies indicated that Stat3 plays an important role in brain metastasis. Here, we present evidence that Stat3 functions at the level of the microenvironment of brain metastases. Stat3 controlled constitutive and inducible VEGFR2 expression in tumor-associated brain endothelial cells. Furthermore, inhibition of Stat3 by WP1066 decreased the incidence of brain metastases and increased survival in a preclinical model of breast cancer brain metastasis. WP1066 inhibited Stat3 activation in tumor-associated endothelial cells, reducing their infiltration and angiogenesis. WP1066 also inhibited breast cancer cell invasion. Our results indicate that WP1066 can inhibit tumor angiogenesis and brain metastasis mediated by Stat3 in endothelial and tumor cells.

KEYWORDS:

Stat3; Stat3 inhibitor; VEGFR2; brain endothelial cells; brain metastasis

PMID:
25881542
PMCID:
PMC4496337
DOI:
10.18632/oncotarget.3540
[Indexed for MEDLINE]
Free PMC Article

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