Listeria monocytogenes promotes tumor growth via tumor cell toll-like receptor 2 signaling.
The contribution of bacterial infection to tumorigenesis is usually ascribed to infection-associated inflammation. An alternate view is that direct interaction of bacteria with tumor cells promotes tumor progression. Here, we show that the microenvironment of large tumors favors bacterial survival, which in turn directly accelerates tumor growth by activating tumor cell Toll-like receptors (TLR). Listeria monocytogenes (Lm) survives in the microenvironment of large but not small tumors, resulting in the promotion of tumor growth. Lm did not affect the percentage of regulatory T cells or myeloid suppressor cells in the tumor. Through TLR2 signaling, Lm activated mitogen-activated protein kinases and nuclear factor-kappaB in tumor cells, resulting in the increased production of nitric oxide and interleukin-6 and increased proliferation of tumor cells. All of these effects were abrogated by silencing expression of TLR2, but not TLR4. The interaction of Helicobacter pylori with tumor cells from gastric carcinoma patients resulted in similar effects. These findings provide a new insight into infection-associated tumorigenesis and illustrate the importance of antibiotic therapy to treat tumors with bacterial infiltration.
Huang
Bo
B
Department of Biochemistry and Molecular Biology, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, The People's Republic of China.
Zhao
Jie
J
Shen
Shiqian
S
Li
Hongxing
H
He
Kai-Li
KL
Shen
Guan-Xin
GX
Mayer
Lloyd
L
Unkeless
Jay
J
Li
Dong
D
Yuan
Ye
Y
Zhang
Gui-Mei
GM
Xiong
Huabao
H
Feng
Zuo-Hua
ZH
D000818:Animals; D006528:Carcinoma, Hepatocellular / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D048708:Cell Growth Processes / Q000502:physiology; D045744:Cell Line, Tumor; D004789:Enzyme Activation; D016480:Helicobacter pylori / Q000502:physiology; D006801:Humans; D007694:Killer Cells, Natural / Q000276:immunology; D008089:Listeria monocytogenes / Q000276:immunology / Q000502:physiology*; D008113:Liver Neoplasms / Q000276:immunology / Q000378:metabolism / Q000382:microbiology* / Q000473:pathology; D051379:Mice; D008807:Mice, Inbred BALB C; D020928:Mitogen-Activated Protein Kinases / Q000378:metabolism; D016328:NF-kappa B / Q000378:metabolism; D015398:Signal Transduction; D013274:Stomach Neoplasms / Q000382:microbiology; D051195:Toll-Like Receptor 2 / Q000378:metabolism*
D016328:NF-kappa B; D051195:Toll-Like Receptor 2; D020928:Mitogen-Activated Protein Kinases