Expression of Irisin/FNDC5 in Cancer Cells and Stromal Fibroblasts of Non-small Cell Lung Cancer

Abstract

Background: Recent in vitro studies have indicated that irisin inhibits proliferation, migration and epithelial-mesenchymal transition. Irisin expression has not been studied in tumour tissues of non-small cell lung cancer (NSCLC) patients yet. The aim of the study was to determine the irisin expression in NSCLCs in comparison to the clinicopathological factors and expression of TTF-1, p63 and Ki-67. Material and methods: Tissue microarrays with 729 NSCLC and 140 non-malignant lung tissue (NMLT) were used to perform immunohistochemical reactions. Laser Capture Microdissection (LCM) was used to collect cancer and stromal cells from NSCLCs. FNDC5 expression was tested for LCM samples, 75 NSCLCs and 25 NMLTs with the RT-PCR technique. Western-blot, immunofluorescence reaction and RT-PCR assays were performed on lung cancer cell lines. Results: Irisin expression was observed in NSCLC cancer cells and stromal fibroblasts. In cancer cells, irisin expression was decreased in higher grades (G) of malignancy, tumour size (T) and according to lymph node metastasis. In stromal cells, irisin expression was increased in higher G and advanced T. A shorter overall survival was observed in patients with higher irisin expression in NSCLC stromal cells. Conclusions: Irisin expression in stromal fibroblasts may influence cancer cell proliferation and may be a prognostic factor for survival in NSCLC.

Myokines in treatment-naïve patients with cancer-associated cachexia

“…In spite of this increase amount of irisin within tumors, lower serum concentration of irisin has been reported in patients with colorectal [26] and breast cancer [27], compared to healthy subjects. In the non-small cell lung carcinoma, irisin was detected in the cytoplasm of cancer cells and in the cytoplasm of tumor stromal cells, but not in normal lung parenchyma [68]. The increased content in tumor cells may be due to the higher glycolytic rate in such cells, as in muscle cells irisin seems to increase glucose uptake by enhancing p38 mitogen-activated protein kinase activation, through AMPKa2 and GLUT4 translocation to the plasma membrane [71].…”

“…We found that irisin protein expression was higher in the tumor samples from CC, in relation to WSC. Lung [68], liver [69] and other gastrointestinal tumors [70] also were shown to express a high content of irisin. In spite of this increase amount of irisin within tumors, lower serum concentration of irisin has been reported in patients with colorectal [26] and breast cancer [27], compared to healthy subjects.…”

Diffusion Kurtosis Imaging—A Superior Approach to Assess Tumor–Stroma Ratio in Pancreatic Ductal Adenocarcinoma

“…The components of the desmoplastic stroma, such as type I collagen, have been described to enhance proliferation of PDAC cells [ 5 ], to increase invasion of tumor cells and to contribute to drug resistance by increasing expression of membrane-type 1 matrix metalloproteinase (MT1-MMP) [ 6 , 7 ]. The tumor-promoting effects of the tumor stroma was not exclusively shown for PDAC, but also for other cancers, such as lung or colon cancer [ 8 , 9 , 10 ].…”

<p>Review of Research on the Role of Irisin in Tumors</p>

“…[30] Lung cancer Protein increase Irisin may be a prognostic factor for survival in non-small cell lung cancer. [31] Irisin inhibits epithelial-mesenchymal transition and reduces the invasion of lung cancer cells via the PI3K/AKT/Snail pathway.…”

“…Katarzyna et al 31 found that irisin was elevated in the cancer cells and tumor stromal fibroblasts of patients with non-small cell lung cancer (NSCLC). The expression levels of irisin in cancer cells vary between NSCLC subtypes, eg, the expression levels are higher in adenocarcinoma (AC) than in squamous-cell carcinoma (SCC).…”