CCR4 promotes metastasis via ERK/NF-κB/MMP13 pathway and acts downstream of TNF-α in colorectal cancer

Ou, Baochi; Zhao, Jingkun; Guan, Shaopei; Feng, Hao; Wangpu, Xiongzhi; Zhu, Congcong; Zong, Yaping; Ma, Junjun; Sun, Jing Ping; Shen, Xiaohui; Liu, Aiguo

doi:10.18632/oncotarget.10256

Cited by 41 publications

(32 citation statements)

References 36 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…As one possible mechanism, it could be that macrophage-derived CCL17 activates directly CCR4-expressing fibroblasts, which in turn augment MMP3 and MMP13 expression, leading to joint damage -both MMPs are expressed in synovial tissue from patients with early symptomatic OA [55]. Notably, CCL17-mediated CCR4 activation in other models is reported to up-regulate MMP13 [56,57]. Importantly, cells in both cartilage and bone are also likely to express MMPs [58] and whether CCL17 acts directly on cartilage and bone requires further investigation, as does the relative contribution of the synovium, cartilage and bone to pain and joint destruction in this model.…”

Section: Discussionmentioning

confidence: 99%

CCL17 blockade as a therapy for osteoarthritis pain and disease

Lee

Salem

Achuthan

et al. 2020

Osteoarthritis and Cartilage

View full text Add to dashboard Cite

Background: Granulocyte macrophage-colony stimulating factor (GM-CSF) has been implicated in the pathogenesis of a number of inflammatory diseases and in osteoarthritis (OA). We identified previously a new GM-CSF→Jmjd3→interferon regulatory factor 4 (IRF4)→chemokine (c-c motif) ligand 17 (CCL17) pathway, which is important for the development of inflammatory arthritis pain and disease. Tumour necrosis factor (TNF) can also be linked with this pathway. Here we investigated the involvement of the pathway in OA pain and disease development using the GM-CSF-dependent collagenase-induced OA (CiOA) model. Methods: CiOA was induced in C57BL/6 wild-type (WT), Irf4 −/− , Ccl17 E/E , Ccr4 −/− , Tnf −/− and GM-CSF −/− mice. Additionally, therapeutic targeting of CCL17, Jmjd3 and cyclooxygenase 2 (COX-2) was evaluated. Development of pain (assessment of weight distribution) and OA disease (histologic scoring of synovitis, cartilage destruction and osteophyte size) were assessed. Synovial joint cells, including neutrophils, macrophages, fibroblasts and endothelial cells, were isolated (cell sorting) and gene expression analyzed (quantitative PCR). Results: Studies in the gene-deficient mice indicated that IRF4, CCL17 and the CCL17 receptor, CCR4, but not TNF, were required for CiOA pain and optimal cartilage destruction and osteophyte size. Therapeutic neutralization of CCL17 and Jmjd3 ameliorated both pain and disease, whereas the COX-2 inhibitor only ameliorated pain. In the synovium Ccl17 mRNA was expressed only in the macrophages in a GM-CSF-dependent and IRF4-dependent manner. Conclusions: The GM-CSF→Jmjd3→IRF4→CCL17 pathway is important for the development of CiOA, with CCL17 thus being a potential therapeutic target for the treatment of both OA pain and disease.

show abstract

Section: Discussionmentioning

confidence: 99%

CCL17 blockade as a therapy for osteoarthritis pain and disease

Lee

Salem

Achuthan

et al. 2020

Osteoarthritis and Cartilage

View full text Add to dashboard Cite

show abstract

“…MMP‐2/‐9 plays important roles in cancer invasion and metastasis . MMP13 plays an important role in CCR4‐mediated cancer cell invasion, which is upregulated by ERK/NF‐κB signaling . FN1 is an extracellular matrix protein which promotes the adhesion, survival, migration, and differentiation of cells, and it has been shown to play an important role in wound healing and embryonic development …”

Section: Discussionmentioning

confidence: 99%

Ouabain impairs cell migration, and invasion and alters gene expression of human osteosarcoma U‐2 OS cells

Shih¹,

Liu³

et al. 2017

Environmental Toxicology

View full text Add to dashboard Cite

Ouabain, the specific Na /K -ATPase blocker, has biological activity including anti-proliferative and anti-metastasis effects in cancer cell. There is no study to show ouabain inhibiting cell migration and invasion in human osteosarcoma U-2 OS cells. Thus, we investigated the effect of ouabain on the cell migration and invasion of human osteosarcoma U-2 OS cells. Results indicated that ouabain significantly decreased the percentage of viable cells at 2.5-5.0 μM, thus, we selected 0.25-1.0 μM for inhibiting studies. Ouabain inhibited cell migration, invasion and the enzymatic activities of MMP-2, and also affected the expression of metastasis-associated protein in U-2 OS cells. The cDNA microarray assay indicated that CDH1, TGFBR3, SHC3 and MAP2K6 metastasis-related genes were increased, but CCND1, JUN, CDKN1A, TGFB1, 2 and 3, SMAD4, MMP13, MMP2 and FN1 genes were decreased. These findings provide more information regarding ouabain inhibited cell migration and invasion and associated gene expressions in U-2 OS cells after exposed to ouabain.

show abstract

“…Although these cell lines were of the same genetic background, primary tumor-derived cells expressed low levels of the chemokine receptor CCR4, whereas brain-metastasizing melanoma cells expressed significantly higher levels of CCR4. CCR4 has already been shown to direct organ-specific metastasis of breast, colorectal, and gastric cancers [ 20 , 21 , 22 ]. Furthermore, “brain-derived soluble factors” upregulate CCR4 expression in melanoma cells and enhance the migration of brain-metastasizing melanoma cells specifically; however, whether these soluble factors are the brain-expressed CCR4 ligands, CCL17 or CCL22, and whether this signaling axis promotes melanoma brain metastasis remains to be determined [ 23 ].…”

Section: Mechanisms Of Melanoma Brain Metastasismentioning

confidence: 99%

Melanoma Brain Metastasis: Mechanisms, Models, and Medicine

Kircher

Silvis

Cho

et al. 2016

IJMS

View full text Add to dashboard Cite

The development of brain metastases in patients with advanced stage melanoma is common, but the molecular mechanisms responsible for their development are poorly understood. Melanoma brain metastases cause significant morbidity and mortality and confer a poor prognosis; traditional therapies including whole brain radiation, stereotactic radiotherapy, or chemotherapy yield only modest increases in overall survival (OS) for these patients. While recently approved therapies have significantly improved OS in melanoma patients, only a small number of studies have investigated their efficacy in patients with brain metastases. Preliminary data suggest that some responses have been observed in intracranial lesions, which has sparked new clinical trials designed to evaluate the efficacy in melanoma patients with brain metastases. Simultaneously, recent advances in our understanding of the mechanisms of melanoma cell dissemination to the brain have revealed novel and potentially therapeutic targets. In this review, we provide an overview of newly discovered mechanisms of melanoma spread to the brain, discuss preclinical models that are being used to further our understanding of this deadly disease and provide an update of the current clinical trials for melanoma patients with brain metastases.

show abstract

CCR4 promotes metastasis via ERK/NF-κB/MMP13 pathway and acts downstream of TNF-α in colorectal cancer

Cited by 41 publications

References 36 publications

CCL17 blockade as a therapy for osteoarthritis pain and disease

CCL17 blockade as a therapy for osteoarthritis pain and disease

Ouabain impairs cell migration, and invasion and alters gene expression of human osteosarcoma U‐2 OS cells

Melanoma Brain Metastasis: Mechanisms, Models, and Medicine

Contact Info

Product

Resources

About