Abstract
Despite advances in early diagnosis and multimodality therapy for cancers, most of lung cancer patients have been locally advanced or metastatic at the time of diagnosis, suggesting the highly progressive characteristic of lung cancer cells. The mechanisms underling invasiveness and metastasis of lung cancer are yet to be elucidated. In the present study, immunohistochemistry was performed to detect the expression of CXCL16-CXCR6 in human lung cancer tissues. It was demonstrated that similar to CXCL12 and CXCR4, CXCL16 and CXCR6 were also coexpressed in human primary lung cancer tissues. After confirming the functional existence of CXCL16 and CXCR6 protein in A549, 95D and H292 cells by ELSA and flow cytometry analysis, we further explored the significance of CXCL16-CXCR6 axis in the biological functions of lung cancer cell lines in vitro. It was found that CXCL16 had no effects on the PCNA (proliferating cell nuclear antigen) expression of A549, 95D and H292 cells. However, both exogenous CXCL16 and CM (conditioned medium from A549, 95D or H292) significantly improved the in vitro viability and invasion of three lung cancer cell lines. The neutralizing antibody to CXCL16 or down-regulation of CXCR6 was able to inhibit the increased viability and invasiveness of A549, 95D and H292 cells stimulated by CXCL16 or CM. Our results imply that CXCL16-CXCR6 axis is involved in the regulation of viability and invasion rather than PCNA expression of lung caner cells, which opens the door for better understanding the mechanisms of lung tumor progression and metastasis.
Publication types
-
Research Support, Non-U.S. Gov't
MeSH terms
-
Adenocarcinoma, Bronchiolo-Alveolar / genetics
-
Adenocarcinoma, Bronchiolo-Alveolar / metabolism
-
Adenocarcinoma, Bronchiolo-Alveolar / pathology*
-
Apoptosis
-
Blotting, Western
-
Carcinoma, Adenosquamous / genetics
-
Carcinoma, Adenosquamous / metabolism
-
Carcinoma, Adenosquamous / pathology*
-
Carcinoma, Squamous Cell / genetics
-
Carcinoma, Squamous Cell / metabolism
-
Carcinoma, Squamous Cell / pathology*
-
Cell Differentiation
-
Cell Movement*
-
Cell Proliferation
-
Chemokine CXCL16
-
Chemokines, CXC / antagonists & inhibitors
-
Chemokines, CXC / genetics
-
Chemokines, CXC / metabolism*
-
Enzyme-Linked Immunosorbent Assay
-
Flow Cytometry
-
Humans
-
Immunoenzyme Techniques
-
In Vitro Techniques
-
Lung Neoplasms / genetics
-
Lung Neoplasms / metabolism
-
Lung Neoplasms / pathology*
-
Neoplasm Invasiveness
-
RNA, Messenger / genetics
-
RNA, Small Interfering / genetics
-
Real-Time Polymerase Chain Reaction
-
Receptors, CXCR6
-
Receptors, Chemokine / antagonists & inhibitors
-
Receptors, Chemokine / genetics
-
Receptors, Chemokine / metabolism*
-
Receptors, Scavenger / antagonists & inhibitors
-
Receptors, Scavenger / genetics
-
Receptors, Scavenger / metabolism*
-
Receptors, Virus / antagonists & inhibitors
-
Receptors, Virus / genetics
-
Receptors, Virus / metabolism*
-
Reverse Transcriptase Polymerase Chain Reaction
-
Tumor Cells, Cultured
Substances
-
CXCL16 protein, human
-
CXCR6 protein, human
-
Chemokine CXCL16
-
Chemokines, CXC
-
RNA, Messenger
-
RNA, Small Interfering
-
Receptors, CXCR6
-
Receptors, Chemokine
-
Receptors, Scavenger
-
Receptors, Virus
Grants and funding
This work is supported by National Natural Science Foundation of China 81270753 (to W.-H.Z.), Wuhan Science and Technology Project 2013060602010249 (to W.-D.H.), Natural Science Foundation of Science and Technology Ministry of Hubei Province 2010CDB05502 (to W.-D.H.) and Personnel Training Plan of The Health Care System of Beijing 2013-3-021 (to W.-H.Z.). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.