Abstract
Thrombopoietin (TPO) is a haematopoietic cytokine mainly produced by the liver and kidneys, which stimulates the production and maturation of megakaryocytes. In the past decade, numerous studies have investigated the effects of TPO outside the haematopoietic system; however, the role of TPO in the progression of solid cancer, particularly lung cancer, has not been well studied. Exogenous TPO does not affect non‐small‐cell lung cancer (NSCLC) cells as these cells show no or extremely low TPO receptor expression; therefore, in this study, we focused on endogenous TPO produced by NSCLC cells. Immunohistochemical analysis of 150 paired NSCLC and adjacent normal tissues indicated that TPO was highly expressed in NSCLC tissues and correlated with clinicopathological parameters including differentiation, P‐TNM stage, lymph node metastasis and tumour size. Suppressing endogenous TPO by small interfering RNA inhibited the proliferation and migration of NSCLC cells. Moreover, TPO interacted with the EGFR protein and delayed ligand‐induced EGFR degradation, thus enhancing EGFR signalling. Notably, overexpressing TPO in EGF‐stimulated NSCLC cells facilitated cell proliferation and migration, whereas no obvious changes were observed without EGF stimulation. Our results suggest that endogenous TPO promotes tumorigenicity of NSCLC via regulating EGFR signalling and thus could be a therapeutic target for treating NSCLC.
Highlights
Lung cancer is the leading cause of cancer-related deaths worldwide.[1]
The lack of TPO receptor (C-MPL) is implicated in most solid tumour cells including non-small-cell lung carcinoma (NSCLC) cells, and these are not affected by exogenous TPO that acts by binding to this receptor.[9,10,11]
Cell Counting Kit-8 (CCK-8) and Transwell results showed that rh-TPO does not affect the proliferation or migration of these two cells (Figure S1B,C)
Summary
Lung cancer is the leading cause of cancer-related deaths worldwide.[1]. There are two main subtypes of lung cancer, small-cell lung carcinoma and non-small-cell lung carcinoma (NSCLC), with NSCLC accounting for approximately 85% of all cases.[2]. We found that TPO is highly expressed in most NSCLC cell lines compared to HBE cells at both the mRNA and protein levels but not secreted to the medium. The results of the CCK-8, colony formation and Transwell assays for A549 and H1299 cells transfected with the TPO plasmid showed no significant differences compared to the control groups (data not shown).
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