Streptococcus pneumoniae promotes lung cancer development and progression

Abstract

<i>Streptococcus pneumoniae (SP)</i> is associated with lung cancer, yet its role in the tumorigenesis remains uncertain. Herein we find that <i>SP</i> attaches to lung cancer cells via binding pneumococcal surface protein C (PspC) to platelet-activating factor receptor (PAFR). Interaction between PspC and PAFR stimulates cell proliferation and activates PI3K/AKT and nuclear factor kB (NF-kB) signaling pathways, which trigger a pro-inflammatory response. Lung cancer cells infected with <i>SP</i> form larger tumors in BALB/C mice compared to untreated cells. Mice treated with tobacco carcinogen and <i>SP</i> develop more lung tumors and had shorter survival period than mice treated with the carcinogen alone. Mutating PspC or PAFR abolishes tumor-promoting effects of <i>SP</i>. Overabundance of <i>SP</i> is associated with the survival. <i>SP</i> may play a driving role in lung tumorigenesis by activating PI3K/AKT and NF-kB pathways via binding PspC to PAFR and provide a microbial target for diagnosis and treatment of the disease.