Int. J. Mol. Sci. 2013, 14(5), 10090-10106; doi:10.3390/ijms140510090
Article

Vascular Endothelial Growth Factor Induces CXCL1 Chemokine Release via JNK and PI-3K-Dependent Pathways in Human Lung Carcinoma Epithelial Cells

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Received: 2 February 2013; in revised form: 23 April 2013 / Accepted: 2 May 2013 / Published: 10 May 2013
(This article belongs to the Special Issue Signalling Molecules and Signal Transduction in Cells)
This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.
Abstract: Lung cancer cells express different chemokines and chemokine receptors that modulate leukocyte infiltration within tumor microenvironment. In this study we screened several mediators/growth factors on CXCL1 release in human carcinoma epithelial cells. Of the tested mediators, VEGF was found to have a robust increase in causing CXCL1 release. VEGF stimulated CXCL1 release and mRNA expression in a time- and concentration-dependent manner. The release was inhibited by the VEGF receptor antagonists and the JNK, PI-3K, tyrosine kinase, and transcription inhibitors. In parallel, VEGF induced JNK, PI3K and Akt activation. Strikingly, among these inhibitors only the JNK inhibitor could reduce VEGF-induced CXCL1 mRNA expression, suggesting that JNK participated in VEGF-induced CXCL1 synthesis, whereas PI-3K was responsible for cellular CXCL1 secretory process. In addition, the steroid dexamethasone and TGF-β suppressed CXCL1 release through a transcriptional regulation. We also showed that cells stimulated with VEGF significantly attracted monocyte migration, which could be abolished by CXCL1 B/N Ab, CXC receptor 2 antagonist, TGF-β, and dexamethasone. In summary, we provide here evidence showing JNK activation for VEGF-induced CXCL1 DNA transcription and PI-3K pathway for extracellular CXCL1 release in human carcinoma epithelial cells. The released CXCL1 was functionally linked to recruiting monocytes into lung cancer cell microenvironment.
Keywords: A549; chemokine; CXCL1; GRO alpha; signaling; VEGF
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MDPI and ACS Style

Lo, H.-M.; Shieh, J.-M.; Chen, C.-L.; Tsou, C.-J.; Wu, W.-B. Vascular Endothelial Growth Factor Induces CXCL1 Chemokine Release via JNK and PI-3K-Dependent Pathways in Human Lung Carcinoma Epithelial Cells. Int. J. Mol. Sci. 2013, 14, 10090-10106.

AMA Style

Lo H-M, Shieh J-M, Chen C-L, Tsou C-J, Wu W-B. Vascular Endothelial Growth Factor Induces CXCL1 Chemokine Release via JNK and PI-3K-Dependent Pathways in Human Lung Carcinoma Epithelial Cells. International Journal of Molecular Sciences. 2013; 14(5):10090-10106.

Chicago/Turabian Style

Lo, Huey-Ming; Shieh, Jiunn-Min; Chen, Chih-Li; Tsou, Chih-Jen; Wu, Wen-Bin. 2013. "Vascular Endothelial Growth Factor Induces CXCL1 Chemokine Release via JNK and PI-3K-Dependent Pathways in Human Lung Carcinoma Epithelial Cells." Int. J. Mol. Sci. 14, no. 5: 10090-10106.

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