Abstract
Poor clinical outcome of lung cancer (LuCa) is primarily due to lack of knowledge about specific molecules involved in its progression and metastasis. In this study, we for the first time show the clinical and biological significance of CC chemokine receptor-9 (CCR9) in non-small cell lung cancer (NSCLC). Expression of CCR9 and CCL25, the only natural ligand of CCR9, was significantly higher (p<0.0001) in NSCLC tissues and serum respectively, compared to their respective controls. Interestingly, expression of both CCR9 and CCL25 was significantly higher in adenocarcinomas (ACs) compared to squamous cell carcinomas (SCCs) (p = 0.04, and p< 0.0001). Similar to tissues, AC and SCC cell lines were positive for CCR9 expression. Despite of marginal difference in CCR9 expression, AC cells showed higher migratory and invasive potential in response to CCL25, compared to SCC cells. This differential biological response of AC cells was primarily due to differential expression of matrix metalloproteinases and tissue inhibitor of metalloproteinases under the influence of CCL25. Our results suggest CCR9 as a potential target for developing new treatment modality for NSCLC. Additionally, differential serum CCL25 level in ACs and SCCs, two NSCLC subtypes, suggest its potential as a non-invasive diagnostic/prognostic biomarker.
Highlights
Lung cancer (LuCa) is a leading cause of death for both men and women worldwide, with an estimated 159,260 deaths (86,930 men and 72,330 women) in the United States in 2014 (American Cancer Society)
Among all chemokine receptors known to be involved in the progression of different cancers including LuCa, CXCR4 is expressed in majority of cancers and plays an important role in dissemination and homing of primary tumor at distant sites [6,2225]
In this study for the first time we have shown the potential role of chemokine receptor-9 (CCR9) in LuCa, which was highly expressed in non-small cell lung carcinoma (NSCLC) tissues compared to controls
Summary
Lung cancer (LuCa) is a leading cause of death for both men and women worldwide, with an estimated 159,260 deaths (86,930 men and 72,330 women) in the United States in 2014 (American Cancer Society). NSCLC, which accounts for 85% of lung cancer cases, have two most common subtypes i.e. squamous cell carcinoma (SCC) and adenocarcinoma (AC). The latter form of the disease accounts for about 40% of all NSCLC cases and has a poorer prognosis relative to SCC [1,4]. The molecular mechanisms involved in the metastatic process and factors involved in disseminating primary tumor and directing disseminated cells to specific organs are not fully elucidated. This process shares similarities with immune cell trafficking, which is primarily mediated by chemokinechemokine receptors
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