Next Article in Journal
Functional Divergence of Poplar Histidine-Aspartate Kinase HK1 Paralogs in Response to Osmotic Stress
Next Article in Special Issue
Alterations of Epigenetic Regulators in Pancreatic Cancer and Their Clinical Implications
Previous Article in Journal
Roles of Erythroid Differentiation Regulator 1 (Erdr1) on Inflammatory Skin Diseases
Previous Article in Special Issue
Serum Soluble Fms-Like Tyrosine Kinase 1 (sFlt-1) Predicts the Severity of Acute Pancreatitis
Article

Toll Like Receptor 2, 4, and 9 Signaling Promotes Autoregulative Tumor Cell Growth and VEGF/PDGF Expression in Human Pancreatic Cancer

1
Department of Surgery I, Molecular Oncology and Immunology, University of Wuerzburg, 97080 Wuerzburg, Germany
2
Surgical Clinic Mannheim, University of Heidelberg, 68167 Mannheim, Germany
3
Medical School, Evangelic Faculty of Paraná, 80730-000 Curitiba, Brazil
4
Brigham and Women’s Hospital, Transplant Research Center, Harvard Medical School, Boston, MA 02115, USA
5
Department of Surgery I, University of Wuerzburg, 97080 Wuerzburg, Germany
*
Author to whom correspondence should be addressed.
These authors contributed equally to this work.
Academic Editors: Srikumar Chellappan and Jaya Padmanabhan
Int. J. Mol. Sci. 2016, 17(12), 2060; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17122060
Received: 10 October 2016 / Revised: 23 November 2016 / Accepted: 2 December 2016 / Published: 8 December 2016
(This article belongs to the Special Issue Pancreatic Disorders)
Toll like receptor (TLR) signaling has been suggested to play an important role in the inflammatory microenvironment of solid tumors and through this inflammation-mediated tumor growth. Here, we studied the role of tumor cells in their process of self-maintaining TLR expression independent of inflammatory cells and cytokine milieu for autoregulative tumor growth signaling in pancreatic cancer. We analyzed the expression of TLR2, -4, and -9 in primary human cancers and their impact on tumor growth via induced activation in several established pancreatic cancers. TLR-stimulated pancreatic cancer cells were specifically investigated for activated signaling pathways of VEGF/PDGF and anti-apoptotic Bcl-xL expression as well as tumor cell growth. The primary pancreatic cancers and cell lines expressed TLR2, -4, and -9. TLR-specific stimulation resulted in activated MAP-kinase signaling, most likely via autoregulative stimulation of demonstrated TLR-induced VEGF and PDGF expression. Moreover, TLR activation prompted the expression of Bcl-xL and has been demonstrated for the first time to induce tumor cell proliferation in pancreatic cancer. These findings strongly suggest that pancreatic cancer cells use specific Toll like receptor signaling to promote tumor cell proliferation and emphasize the particular role of TLR2, -4, and -9 in this autoregulative process of tumor cell activation and proliferation in pancreatic cancer. View Full-Text
Keywords: TLR2; TLR4; TLR9; pancreatic cancer; inflammation; tumor growth TLR2; TLR4; TLR9; pancreatic cancer; inflammation; tumor growth
Show Figures

Graphical abstract

MDPI and ACS Style

Grimmig, T.; Moench, R.; Kreckel, J.; Haack, S.; Rueckert, F.; Rehder, R.; Tripathi, S.; Ribas, C.; Chandraker, A.; Germer, C.T.; Gasser, M.; Waaga-Gasser, A.M. Toll Like Receptor 2, 4, and 9 Signaling Promotes Autoregulative Tumor Cell Growth and VEGF/PDGF Expression in Human Pancreatic Cancer. Int. J. Mol. Sci. 2016, 17, 2060. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17122060

AMA Style

Grimmig T, Moench R, Kreckel J, Haack S, Rueckert F, Rehder R, Tripathi S, Ribas C, Chandraker A, Germer CT, Gasser M, Waaga-Gasser AM. Toll Like Receptor 2, 4, and 9 Signaling Promotes Autoregulative Tumor Cell Growth and VEGF/PDGF Expression in Human Pancreatic Cancer. International Journal of Molecular Sciences. 2016; 17(12):2060. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17122060

Chicago/Turabian Style

Grimmig, Tanja, Romana Moench, Jennifer Kreckel, Stephanie Haack, Felix Rueckert, Roberta Rehder, Sudipta Tripathi, Carmen Ribas, Anil Chandraker, Christoph T. Germer, Martin Gasser, and Ana M. Waaga-Gasser. 2016. "Toll Like Receptor 2, 4, and 9 Signaling Promotes Autoregulative Tumor Cell Growth and VEGF/PDGF Expression in Human Pancreatic Cancer" International Journal of Molecular Sciences 17, no. 12: 2060. https://0-doi-org.brum.beds.ac.uk/10.3390/ijms17122060

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop