Premium
Gram‐positive pneumonia augments non‐small cell lung cancer metastasis via host toll‐like receptor 2 activation
Author(s) -
Gowing Stephen D.,
Chow Simon C.,
CoolsLartigue Jonathan J.,
Chen Crystal B.,
Najmeh Sara,
Jiang Henry Y.,
Bourdeau France,
Beauchamp Annie,
Mancini Ugo,
Angers Isabelle,
Giannias Betty,
Spicer Jonathan D.,
Rousseau Simon,
Qureshi Salman T.,
Ferri Lorenzo E.
Publication year - 2017
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.30734
Subject(s) - tlr2 , metastasis , lipoteichoic acid , biology , in vivo , cancer research , lung cancer , immunology , pneumonia , a549 cell , innate immune system , receptor , toll like receptor , medicine , cancer , immune system , pathology , staphylococcus aureus , genetics , microbiology and biotechnology , bacteria , biochemistry
Surgical resection of early stage nonsmall cell lung cancer (NSCLC) is necessary for cure. However, rates of postoperative bacterial pneumonias remain high and may confer an increased risk for metastasis. Toll‐like receptors (TLRs) mediate the inflammatory cascade by recognizing microbial products at the surface of numerous cell types in the lung; however, little is known about how host TLRs influence NSCLC metastasis. TLR2 recognizes gram‐positive bacterial cell wall components activating innate immunity. We demonstrate that lower respiratory tract infection with Streptococcus pneumonia augments the formation of murine H59 NSCLC liver metastases in C57BL/6 mice through host TLR2 activation. Infected mice demonstrate increased H59 and human A549 NSCLC adhesion to hepatic sinusoids in vivo compared with noninfected controls, a response that is significantly diminished in TLR2 knock‐out mice. Intra‐tracheal injection of purified TLR2 ligand lipoteichoic acid into mice similarly augments in vivo adhesion of H59 cells to hepatic sinusoids. Additionally, H59 and A549 NSCLC cells incubated with bronchoepithelial conditioned media show increased cell adhesion to extracellular matrix components in vitro and hepatic sinusoids in vivo in a manner that is dependent on bronchoepithelial TLR2 activation and interleukin‐6 secretion. TLR2 is therefore a potential therapeutic target for gram‐positive pneumonia‐driven NSCLC metastasis.