Pro-tumoural CXCL10/CXCR3-A autocrine loop in invasive mucinous lung adenocarcinoma
نویسندگان
چکیده
Invasive mucinous adenocarcinoma (IMA) is a mucinous variant of lepidic predominant lung adenocarcinoma (LPA) and associated with a worse prognosis. We postulated that cytokine expression would enable us to differentiate IMA from LPA in terms of prognosis and acquisition of pro-tumoural capacities. A 30-cytokine panel was assessed in bronchoalveolar lavage fluids (BALF) from IMA (n=38), LPA (n=25) and control samples (n=7). We investigated the expression of differentially expressed cytokines and splice variants of their receptors in surgical samples. The presence of EGFR and KRAS mutations were determined. We also examined the expression of cytokines and splice variants of their receptors in different cell lines, exploring their functional impact on signalling pathways, proliferation and migration. Only C-X-C motif chemokine 10 (CXCL10) was differentially expressed, namely overexpressed in IMA BALF compared with LPA. CXCL10 overexpression in BALF was linked to a worse prognosis. In surgical samples, CXCL10 and its receptor C-X-C motif chemokine receptor 3 (CXCR3) were overexpressed in IMA compared to LPA. A pro-tumoural CXCR3-A splice variant was overexpressed in IMA, suggesting a CXCL10/CXCR3-A autocrine loop in IMA. CXCL10 and CXCR3 expression were not correlated with EGFR or KRAS status. CXCL10 up-regulated CXCR3-A expression, Erk1/2 phosphorylation and enhanced migration in the mucinous H2228 cell line. CXCL10/CXCR3-A may play a pro-tumoural role in IMA via an autocrine mechanism.
منابع مشابه
Analysis of TP53 Codon 72 Polymorphism in Mucinous and Non-Mucinous Colorectal Adenocarcinoma in Isfahan, Iran
Background: The tumor suppressor gene TP53 (alias p53) located on chromosome 17 is involved in various cancers. Case-control studies have shown that p53 codon 72 polymorphism modulates the prognosis and susceptibility to various malignancies. We undertook the present study to explore a possible association between mucinous and non-mucinous adenocarcinomas with different genotypes or alleles at ...
متن کاملThe chemokine receptor CXCR3 and its splice variant are expressed in human airway epithelial cells.
Activation of the chemokine receptor CXCR3 by its cognate ligands induces several differentiated cellular responses important to the growth and migration of a variety of hematopoietic and structural cells. In the human respiratory tract, human airway epithelial cells (HAEC) release the CXCR3 ligands Mig/CXCL9, IP-10/CXCL10, and I-TAC/CXCL11. Simultaneous expression of CXCR3 by HAEC would have i...
متن کاملComplete Response of Advanced Invasive Mucinous Adenocarcinoma of the Lung with Gemcitabine and Pemetrexed
In 2011,mucinous bronchioloalveolar carcinoma was reclassified as invasive mucinous adenocarcinoma, mucinous adenocarcinoma in situ,and mucinous minimally invasive adenocarcinoma.A part of the invasive mucinous adenocarcinoma of the lung differentiates to gastric mucous cells, and we term this type of carcinoma gastric-like invasive mucinous adenocarcinoma.However,treatment approaches have not ...
متن کاملTumoral lymphocytic infiltration and expression of the chemokine CXCL10 in breast cancers from the Ontario Familial Breast Cancer Registry.
PURPOSE Breast carcinomas, including basal and hereditary cases, often present with a prominent tumoral lymphocytic infiltrate. Chemokines could play a role in attracting these cells and contribute to tumor progression. We explored tumoral expression of CXCL10 and determined the relationship between CXCL10 and lymphocytic infiltrate in a cohort of breast cancers. EXPERIMENTAL DESIGN Using tis...
متن کامل