title: Mycobacterium tuberculosis H37Rv infected THP-1 cells induce epithelial mesenchymal transition (EMT) in lung adenocarcinoma epithelial cell line (A549).
abstract: Chronic infections of Mycobacterium tuberculosis (MTB) cause oxidative stress, TLR activation and production of inflammatory cytokines and thus can create an environment reinforcing tumorigenesis, progression and metastasis. Epidemiological studies have established a relation between lung cancer and tuberculosis but cellular mechanism is still poorly understood. In present study, we have shown for the first time that MTB infection in human monocytic cell line (THP-1) enhances invasion and induces EMT characteristics in lung adenocarcinoma cell line (A549) during co-culture. After co-culture with MTB infected THP-1 cells A549 cells exhibited morphological and molecular signatures of EMT. During co-culture, expression of inflammatory cytokines like TNF-α, IL-1β and IL-6 was enhanced in the microenvironment of A549 cells in comparison to single culture of A549 cells. Using pharmacological inhibitors of JNK (SP-600125) and p38 MAPK (SB-203580), we demonstrated the involvement of JNK and p38 MAPK in MTB induced EMT induction in A549 cells. To the best of our knowledge this is the first report demonstrating the role of MTB infection in induction of metastasis associated EMT in lung cancer.
authors.affiliation: Radiation Medicine Centre, Bhabha Atomic Research Centre, Mumbai, India.
authors.forename: Pramod Kumar
authors.initials: PK
authors.lastname: Gupta
authors.affiliation: Radiation Medicine Centre, Bhabha Atomic Research Centre, Mumbai, India.
authors.forename: Devavrat
authors.initials: D
authors.lastname: Tripathi
authors.affiliation: Radiation Medicine Centre, Bhabha Atomic Research Centre, Mumbai, India. Electronic address: savita.kulkarni1@gmail.com.
authors.forename: Savita
authors.initials: S
authors.lastname: Kulkarni
authors.affiliation: Radiation Medicine Centre, Bhabha Atomic Research Centre, Mumbai, India.
authors.forename: M G R
authors.initials: MG
authors.lastname: Rajan
mesh_terms: D000230:Adenocarcinoma / Q000276:immunology / Q000382:microbiology* / Q000473:pathology*; D000077192:Adenocarcinoma of Lung; D015153:Blotting, Western; D045744:Cell Line, Tumor; D002465:Cell Movement; D018920:Coculture Techniques; D058750:Epithelial-Mesenchymal Transition / Q000276:immunology*; D006801:Humans; D008175:Lung Neoplasms / Q000276:immunology / Q000382:microbiology* / Q000473:pathology*; D009169:Mycobacterium tuberculosis; D014397:Tuberculosis, Pulmonary / Q000150:complications* / Q000276:immunology; D059016:Tumor Microenvironment / Q000276:immunology
keywords: E-cadherin; Epithelial mesenchymal transition; Invasion; Metastasis; Mycobacterium tuberculosis; Vimentin