Stem cell autocrine CXCL12/CXCR4 stimulates invasion and metastasis of esophageal cancer

Wang, Xingwei; Cao, Yan; Zhang, Shirong; Chen, Zhihui; Fan, Ling; Shen, Xinyong; Zhou, Shiwen; Chen, Dongfeng

doi:10.18632/oncotarget.15254

Cited by 42 publications

(41 citation statements)

References 23 publications

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“…Chemokines and their receptors control cancer development through regulation of leukocyte infiltration, tumourrelated angiogenesis, tumour-specific host immune responses, and cancer cell proliferation and migration [31]. Although the molecular mechanisms underlying cancer metastasis remain to be fully elucidated, accumulating evidence points on a significant role of CXCL12/CXCR4 in the process [32][33][34][35], suggesting that the CXCL12/ CXCR4 axis may be a potential therapeutic target in BC.…”

Section: Discussionmentioning

confidence: 99%

In silico analysis of the immune microenvironment in bladder cancer

Zhang

Zhuang

et al. 2020

BMC Cancer

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Background: Infiltrating immune and stromal cells are vital components of the bladder cancer (BC) microenvironment, which can significantly affect BC progression and outcome. However, the contribution of each subset of tumour-infiltrating immune cells is unclear. The objective of this study was to perform cell phenotyping and transcriptional profiling of the tumour immune microenvironment and analyse the association of distinct cell subsets and genes with BC prognosis. Methods: Clinical data of 412 patients with BC and 433 transcription files for normal and cancer tissues were downloaded from The Cancer Genome Atlas. The CIBERSORT algorithm was used to determine the relative abundance of 22 immune cell types in each sample and the ESTIMATE algorithm was used to identify differentially expressed genes within the tumour microenvironment of BC, which were subjected to functional enrichment and protein-protein interaction (PPI) analyses. The association of cell subsets and differentially expressed genes with patient survival and clinical parameters was examined by Cox regression analysis and the Kaplan-Meier method. Results: Resting natural killer cells and activated memory CD4 + and CD8 + T cells were associated with favourable patient outcome, whereas resting memory CD4 + T cells were associated with poor outcome. Differential expression analysis revealed 1334 genes influencing both immune and stromal cell scores; of them, 97 were predictive of overall survival in patients with BC. Among the top 10 statistically significant hub genes in the PPI network, CXCL12, FN1, LCK, and CXCR4 were found to be associated with BC prognosis. Conclusion: Tumour-infiltrating immune cells and cancer microenvironment-related genes can affect the outcomes of patients and are likely to be important determinants of both prognosis and response to immunotherapy in BC.

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Section: Discussionmentioning

confidence: 99%

In silico analysis of the immune microenvironment in bladder cancer

Zhang

Zhuang

et al. 2020

BMC Cancer

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“…A number of studies have demonstrated that CXCR4/ CXCL12 participates in cancer development (6,8,(15)(16)(17)(18). CXCR4 is the only chemokine receptor expressed by the majority of cancer cells, and its ligand CXCL12 can be secreted by tumor cells and stromal cells, including tumor-associated fibroblasts (24,25).…”

Section: Discussionmentioning

confidence: 99%

“…For example, Lin CH et al (30) demonstrated that CXCL12, acting through CXCR4 and activating the Rac/ERK and JNK signaling pathways, could induce the expression of connective tissue growth factor, which is a profibrotic protein, in human lung fibroblasts, and potentiate their transdifferentiation into myofibroblasts. Wang X et al (16) demonstrated that the autocrine CXCL12/CXCR4 axis can mediate the metastatic property of esophageal cancer stem cells depending on ERK1/2 signaling pathway. Tian Y et al (31) indicated that CXCL12 induced the migration of oligodendrocyte precursor cells via the CXCR4 dependent MEK/ERK and PI3K/AKT pathways.…”

Section: Discussionmentioning

confidence: 99%

“…Within hypoxic areas of malignant tumors, it has been demonstrated that CXCL12 is secreted by a variety of cells, including tumor cells, stromal cells and tumor-associated fibroblasts (4,5). It has been indicated that CXCL12 activates specific tumor cells via autocrine and paracrine signaling, and enhances their proliferation by upregulating CXCR4 expression (15)(16)(17). Furthermore, CXCR4 can facilitate tumor cell adhesion and resistance to apoptosis (17,18).…”

Section: Introductionmentioning

confidence: 99%

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The autocrine CXCR4/CXCL12 axis contributes to lung fibrosis through modulation of lung fibroblast activity

Geng

et al. 2020

Exp Ther Med

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12 (CXCR4/CXCL12) axis has been implicated in the pathogenesis of pulmonary fibrosis. However, the mechanisms governing this remain to be determined. The current study demonstrated that human lung fibroblasts (HLFs) exhibit high CXCL12 expression and also exhibit high expression of its corresponding receptor CXCR4. Exogenous CXCL12 was revealed to significantly promote the migration and proliferation of HLFs, and potentiate CXCR4 expression. These effects were demonstrated to be inhibited by AMD3100, which is an antagonist of CXCR4. Lung and bronchoalveolar lavage fluid CXCR4 and CXCL12 expression was upregulated by in vivo bleomycin administration, which was partially inhibited by pre-treatment with AMD3100. AMD3100 also reduced lung collagen content in the bleomycin model. Inhibiting CXCR4 was indicated to ameliorate the lung compliance and resistance of pulmonary fibrosis. In conclusion, the results of the present study suggested that autocrine CXCR4/CXCL12 axis is an important mechanism underlying the pathogenesis of idiopathic pulmonary fibrosis, and may serve as a potential therapeutic target that can be used in the treatment of pulmonary disease.

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“…CXCL12 also regulates the catabolic activity of chondrocytes by stimulating the release of matrix metalloproteinases and aggrecanases in vitro (Kanbe et al, 2002;Chinni et al, 2006;Lu et al, 2016). The CXCL12/CXCR4 axis plays a major role in the repair of cartilage by acting as a chemoattractant for inflammatory and stem cells (Brand et al, 2005;Hu et al, 2013;Wang et al, 2017). The CXCL12/CXCR4 axis may therefore play dual roles in early stage OA.…”

Section: Introductionmentioning

confidence: 99%

AMD3100 Attenuates Post-Traumatic Osteoarthritis by Maintaining Transforming Growth Factor-β1-Induced Expression of Tissue Inhibitor of Metalloproteinase-3 via the Phosphatidylinositol 3-Kinase/Akt Pathway

Shi

et al. 2020

Front. Pharmacol.

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AMD3100 is a small-molecule inhibitor of the C-X-C motif chemokine ligand 12/C-X-C chemokine receptor type 4 (CXCL12/CXCR4) axis, while its role in aggrecan metabolism is unclear. We hypothesized that the AMD3100 modulates the transforming growth factor-b1 (TGF-b1)-induced expression of tissue inhibitor of metalloproteinase-3 (TIMP-3) in chondrocytes. We evaluated expression of CXCL12/CXCR4 and TIMP-3 in the knee joints of rats with and without osteoarthritis (OA) by immunohistochemistry, immunofluorescence, Western blotting, and enzyme-linked immunosorbent assay (ELISA). The rats were divided into sham control, destabilization of the medial meniscus/ AMD3100-treated (DMM/AMD3100-treated), and DMM/phosphate-buffered saline (PBS)treated groups. After 6 weeks, the rats were euthanized and subjected to histological and immunohistochemical analyses. Also, interleukin (IL)-1-pretreated primary chondrocytes were cultured in the presence of empty control (−, −), CXCL12a (+,−), CXCL12a + small interfering RNA (siRNA) CXCR4 (+,+), or CXCL12a + siNC (+NC), and the expression levels of target markers were evaluated by Western blotting and real-time reverse transcription PCR (RT-PCR). The CXCL12/CXCR4 levels were higher, and the expression of TIMP-3 was lower, in the OA rats compared to the healthy control rats. The rats in the DMM/AMD3100treated group revealed a markedly decreased immunological response and mild pathology. Treatment with CXCL12a increased expression of aggrecan and disintegrin and metalloproteinase with thrombospondin motifs-5 (ADAMTS-5) and suppressed that of TIMP-3 in IL-1-pretreated primary chondrocytes. TGF-b1 increased expression of TIMP-3, and this increase was reversed by CXCL12a via the phosphatidylinositol 3-kinase (PI3K)/Akt signaling pathway. Moreover, these effects were inhibited by the CXCR4 antagonist

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Stem cell autocrine CXCL12/CXCR4 stimulates invasion and metastasis of esophageal cancer

Cited by 42 publications

References 23 publications

In silico analysis of the immune microenvironment in bladder cancer

In silico analysis of the immune microenvironment in bladder cancer

The autocrine CXCR4/CXCL12 axis contributes to lung fibrosis through modulation of lung fibroblast activity

AMD3100 Attenuates Post-Traumatic Osteoarthritis by Maintaining Transforming Growth Factor-β1-Induced Expression of Tissue Inhibitor of Metalloproteinase-3 via the Phosphatidylinositol 3-Kinase/Akt Pathway

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