Streptococcus pneumoniae promotes lung cancer development and progression

Ning Li; Huifen Zhou; Van K Holden; Janaki Deepak; Pushpa Dhilipkannah; Nevins W Todd; Sanford A Stass; Feng Jiang

doi:10.1016/j.isci.2022.105923

Streptococcus pneumoniae promotes lung cancer development and progression

iScience. 2023 Jan 4;26(2):105923. doi: 10.1016/j.isci.2022.105923. eCollection 2023 Feb 17.

Authors

Ning Li^{1

2}, Huifen Zhou¹, Van K Holden², Janaki Deepak², Pushpa Dhilipkannah¹, Nevins W Todd², Sanford A Stass¹, Feng Jiang¹

Affiliations

¹ Department of Pathology, University of Maryland School of Medicine, Baltimore, MD, USA.
² Department of Medicine, University of Maryland School of Medicine, Baltimore, MD, USA.

Abstract

Streptococcus pneumoniae (SP) is associated with lung cancer, yet its role in the tumorigenesis remains uncertain. Herein we find that SP 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 SP form larger tumors in BALB/C mice compared to untreated cells. Mice treated with tobacco carcinogen and SP 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 SP. Overabundance of SP is associated with the survival. SP 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.

Keywords: Bacteriology; Cancer systems biology; Cell; Cell biology.

Grants and funding

U01 FD005946/FD/FDA HHS/United States