Human Lung-Resident Macrophages Express and Are Targets of Thymic Stromal Lymphopoietin in the Tumor Microenvironment

Thymic stromal lymphopoietin (TSLP) is a pleiotropic cytokine highly expressed by epithelial cells and several innate and adaptive immune cells. TSLP exerts its biological effects by binding to a heterodimeric complex composed of TSLP receptor (TSLPR) and IL-7Rα. In humans, there are two TSLP isoforms: the short form (sfTSLP), constitutively expressed, and the long form (lfTSLP), which is upregulated in inflammation. TSLP has been implicated in the induction and progression of several experimental and human cancers. Primary human lung macrophages (HLMs), monocyte-derived macrophages (MDMs), and peripheral blood monocytes consitutively expressed sfTSLP mRNA. Incubation of HLMs, MDMs, and monocytes with lipopolysaccharide (LPS) or IL-4, but not with IL-13, induced TSLP release from HLMs. LPS, but not IL-4 or IL-13, induced CXCL8 release from HLMs. LPS, IL-4 alone or in combination with IL-13, induced the expression of lfTSLP, but not of sfTSLP from HLMs. Preincubation of HLMs with IL-4, alone or in combination with IL-13, but not IL-13 alone, synergistically enhanced TSLP release from LPS-activated macrophages. By contrast, IL-4, alone or in combination with IL-13, inhibited LPS-induced CXCL8 release from HLMs. Immunoreactive TSLP was detected in lysates of HLMs, MDMs, and monocytes. Incubation of HLMs with TSLP induced the release of proinflammatory (TNF-α), angiogenic (VEGF-A, angiopoietin 2), and lymphangiogenic (VEGF-C) factors. TSLP, TSLPR, and IL-7Rα were expressed in intratumoral and peritumoral areas of human lung cancer. sfTSLP and lfTSLP mRNAs were differentially expressed in peritumoral and intratumoral lung cancer tissues. The TSLP system, expressed in HLMs, MDMs, and monocytes, could play a role in chronic inflammatory disorders including lung cancer.

Download Full-text

POU2F2 promotes the proliferation and motility of lung cancer cells by activating AGO1

BMC Pulmonary Medicine ◽

10.1186/s12890-021-01476-9 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Ronggang Luo ◽

Yi Zhuo ◽

Quan Du ◽

Rendong Xiao

Keyword(s):

Lung Cancer ◽

Tumor Growth ◽

Cancer Cells ◽

Cancer Progression ◽

Human Lung ◽

Lung Cancer Cells ◽

Human Lung Cancer ◽

Cancer Tissues

Abstract Background To detect and investigate the expression of POU domain class 2 transcription factor 2 (POU2F2) in human lung cancer tissues, its role in lung cancer progression, and the potential mechanisms. Methods Immunohistochemical (IHC) assays were conducted to assess the expression of POU2F2 in human lung cancer tissues. Immunoblot assays were performed to assess the expression levels of POU2F2 in human lung cancer tissues and cell lines. CCK-8, colony formation, and transwell-migration/invasion assays were conducted to detect the effects of POU2F2 and AGO1 on the proliferaion and motility of A549 and H1299 cells in vitro. CHIP and luciferase assays were performed for the mechanism study. A tumor xenotransplantation model was used to detect the effects of POU2F2 on tumor growth in vivo. Results We found POU2F2 was highly expressed in human lung cancer tissues and cell lines, and associated with the lung cancer patients’ prognosis and clinical features. POU2F2 promoted the proliferation, and motility of lung cancer cells via targeting AGO1 in vitro. Additionally, POU2F2 promoted tumor growth of lung cancer cells via AGO1 in vivo. Conclusion We found POU2F2 was highly expressed in lung cancer cells and confirmed the involvement of POU2F2 in lung cancer progression, and thought POU2F2 could act as a potential therapeutic target for lung cancer.

Download Full-text

MicroRNA-7–regulated TLR9 signaling–enhanced growth and metastatic potential of human lung cancer cells by altering the phosphoinositide-3-kinase, regulatory subunit 3/Akt pathway

Molecular Biology of the Cell ◽

10.1091/mbc.e12-07-0519 ◽

2013 ◽

Vol 24 (1) ◽

pp. 42-55 ◽

Cited By ~ 52

Author(s):

Lin Xu ◽

Zhenke Wen ◽

Ya Zhou ◽

Zhongmin Liu ◽

Qinchuan Li ◽

...

Keyword(s):

Lung Cancer ◽

Cancer Cells ◽

Human Lung ◽

Biological Effects ◽

Tumor Biology ◽

Metastatic Potential ◽

Lung Cancer Cells ◽

Human Lung Cancer ◽

Human Lung Cancer Cells ◽

Tlr9 Signaling

Recent evidence shows that microRNAs (miRNAs) contribute to the biological effects of Toll-like receptor (TLR) signaling on various cells. Our previous data showed that TLR9 signaling could enhance the growth and metastatic potential of human lung cancer cells. However, the potential role of miRNAs in the effects of TLR9 signaling on tumor biology remains unknown. In this paper, we first report that TLR9 signaling could reduce intrinsic miR-7 expression in human lung cancer cells. Furthermore, overexpression of miR-7 can significantly inhibit TLR9 signaling–enhanced growth and metastatic potential of lung cancer cells in vitro and in vivo. Notably, we identify phosphoinositide-3-kinase, regulatory subunit 3 (PIK3R3) as a novel target molecule of miR-7 in lung cancer cells by Western blotting and luciferase report assay. Further study shows that miR-7 inhibits the effects of TLR9 signaling on lung cancer cells through regulation of the PIK3R3/Akt pathway. These data suggest that miR-7 could act as a fine-tuner in regulating the biological effects of TLR9 signaling on human lung cancer cells, which might be helpful to the understanding of the potential role of miRNAs in TLR signaling effects on tumor biology.

Download Full-text

Application of cryobiopsy to morphological and immunohistochemical analyses of xenografted human lung cancer tissues and functional blood vessels

Cancer ◽

10.1002/cncr.23701 ◽

2008 ◽

Vol 113 (5) ◽

pp. 1068-1079 ◽

Cited By ~ 29

Author(s):

Nobuhiko Ohno ◽

Nobuo Terada ◽

Yuqin Bai ◽

Sei Saitoh ◽

Tadao Nakazawa ◽

...

Keyword(s):

Lung Cancer ◽

Blood Vessels ◽

Human Lung ◽

Human Lung Cancer ◽

Cancer Tissues ◽

Immunohistochemical Analyses

Download Full-text

Comprehensive Analysis of the Expression and Prognosis for IRXs in Non-small Cell Lung Cancer

10.21203/rs.3.rs-78198/v1 ◽

2020 ◽

Author(s):

Qiongzi Wang ◽

Xueshan Qiu

Keyword(s):

Lung Cancer ◽

Human Lung ◽

Expression Patterns ◽

Human Lung Cancer ◽

Prognostic Indicators ◽

Normal Lung ◽

Kaplan Meier ◽

Go Enrichment ◽

Cancer Tissues ◽

Kaplan Meier Plotter

Abstract Iroquoishomeobox transcription factor family （IRXs）have been increasingly reported to play roles in suppressing or promoting a variety of cancers, however, little is known about their expression and prognostic value in terms of human lung cancer. In this study, Oncomine, GEPIA, Kaplan-Meier plotter, and cBioPortal databases were used to analyze the different expression patterns and prognostic values of six IRXs in NSCLC and examine their related functions and pathways using GO enrichment. Compared with normal lung cancer tissues, the expression of IRX1 and IRX2 in NSCLC tissues was significantly lower and was positively correlated with the 10-year survival rate of patients. Higher expression of IRX4 was related to terminal tumors, and suggested a poor prognosis. It was also found that IRXs may play a tumor-suppressive role in the localization of cytoplasm in NSCLC, while localization in the nucleus suggests a more malignant behavior. Together these results suggest that IRX1 and IRX2 may be prognostic indicators of LUAD, and that IRX4 could be a potential target for LUAD treatment.

Download Full-text