CC motif chemokine ligand 19 suppressed colorectal cancer in vivo accompanied by an increase in IL-12 and IFN-γ

Lü, Jun; Ma, Junjun; Cai, Wei; Wangpu, Xiongzhi; Feng, Hao; Zhao, Jingkun; Guan, Shaopei; Zong, Yaping; Liu, Aiguo

doi:10.1016/j.biopha.2014.12.032

Cited by 16 publications

(11 citation statements)

References 18 publications

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“…Nevertheless, some other studies indicated that CCL19 can modulate anti-tumor responses in lung cancer and ovarian cancer 13 , 14 . Similarly, our previous studies demonstrated that CCL19 inhibited tumorigenesis, metastasis and angiogenesis, and the expression of CCL19 was associated with the prognosis of CRC patients 15 , 16 . However, the potential function of CCL19 expressed in CRC remains to be elucidated.…”

Section: Introductionsupporting

confidence: 68%

“…It has been reported that CCL19 and CCR7 are able to inhibit metastasis in lung cancer and ovarian cancer 13 , 14 . Moreover, our previous studies revealed that low-expression of CCL19 significantly promoted CRC angiogenesis 16 . Consequently, this study mainly focuses on the potential molecular mechanisms and signal pathways underlying CCL19-related tumor angiogenesis.…”

Section: Discussionmentioning

confidence: 95%

“…Stable transfected CRC cells (1 × 10 6 cells) were subcutaneously injected into 4-week-old male nude mice (Institute of Zoology, China Academy of Sciences), as well as CT26 cells were subcutaneously injected into BALB/c mice. In addition, we injected 0.2 μg recombinant mouse CCL19 (rmCCL19, R&D) in the tumor site of BALB/c mice twice a week 16 . Treatments began approximately 10 days later, when tumors were detectable by palpation.…”

Section: Methodsmentioning

confidence: 99%

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CCL19 suppresses angiogenesis through promoting miR-206 and inhibiting Met/ERK/Elk-1/HIF-1α/VEGF-A pathway in colorectal cancer

et al. 2018

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The mechanisms underlying the role of chemokines in tumor angiogenesis is still not fully understood. In this study, we detected the influence of CCL19 on colorectal cancer (CRC) angiogenesis. The expression of CCL19 and CD31 in CRC tissues were detected by immunohistochemistry. Human CRC cell lines SW1116 and SW620 stably transfected with CCL19 lentivirus and CCL19 shRNA, and HUVEC stably transfected with CCR7 shRNA were used in our study. Our study showed that CCL19 was significantly low-expressed in CRC tissues and positively related to highly tumor microvessel density. In vitro, we observed that CCL19 high-expressed SW1116 supernatant was able to inhibit proliferation, migration, and sprouting responses of HUVEC, whereas CCL19 low-expressed SW620 supernatant can promote HUVEC angiogenesis. Additionally, we further demonstrated that these functions maybe achieved through promoting miR-206 thus inhibiting Met/ERK/Elk-1/HIF-1α/VEGF-A pathway in a CCR7-dependent manner. Mice angiogenesis model also confirmed that elevated expression of CCL19 inhibit the angiogenesis of CRC in vivo. In summary, our results supported that CCL19 can inhibit CRC angiogenesis through promoting miR-206 thus inhibiting Met/ERK/Elk-1/HIF-1α/VEGF-A pathway. This may be a novel therapeutic option for anti-vascular treatment in CRC.

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Section: Introductionsupporting

confidence: 68%

Section: Discussionmentioning

confidence: 95%

Section: Methodsmentioning

confidence: 99%

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CCL19 suppresses angiogenesis through promoting miR-206 and inhibiting Met/ERK/Elk-1/HIF-1α/VEGF-A pathway in colorectal cancer

et al. 2018

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“…Sharma et al, 2000) and the recruiting cytokines/chemokines CXCL9, CXCL10, and IFN-γ (Sherven Sharma et al, 2003). In the LoVo model of human colorectal cancer, treatment with recombinant CCL19 suppressed tumor growth in vivo concurrent with increased serum levels of IL-12 and IFN-γ via a T cell-independent mechanism that involved DC and NK cells (Lu et al, 2015). Furthermore, results from non-tumor models support a beneficial role for CCL21 in generating protective Type 1 immune responses.…”

Section: Cues For Tls Developmentmentioning

confidence: 99%

Therapeutic Lymphoid Organogenesis in the Tumor Microenvironment

Weinstein

Storkus

2015

Advances in Cancer Research

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The inflammatory status of the tumor microenvironment (TME) has been heavily investigated in recent years. Chemokine and cytokine signaling pathways such as CCR7, CXCR5, lymphotoxin, and IL-36, which are involved in the generation of secondary lymphoid organs and effector immune responses, are now recognized as having value both as prognostic factors and as immunomodulatory therapeutics in the context of cancer. Furthermore, when produced in the TME, these mediators have been shown to promote the recruitment of immune cells, including T cells, B cells, dendritic cells (DC), and other specialized immune cell subsets such as follicular dendritic cells (FDC) and T follicular helper (Tfh) cells, in association with the formation of “tertiary” lymphoid structures (TLS) within or adjacent to sites of disease. Although TLS are composed of a heterogeneous collection of immune cell types, whose composition differs based on cancer subtype, the qualitative presence of TLS has been shown to represent a biomarker of good prognosis for cancer patients. A comprehensive understanding of the role each of these pathways plays within the TME may support the rational design of future immunotherapies to selectively promote/bolster TLS formation and function, leading to improved clinical outcomes across the vast range of solid cancer types.

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“…In CRC, the study by Kawada et al revealed that CXCR3 could promote cancer metastasis to lymph nodes [8]. Our previous studies showed that CCL19 suppressed tumorigenesis and metastasis, and the expression of CCL19 was related to the prognosis of patients with colorectal cancer [9, 10]. …”

Section: Introductionmentioning

confidence: 99%

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

Zhao

Guan

et al. 2016

Oncotarget

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Chemokines and chemokine receptors are causally involved in the metastasis of human malignancies. As a crucial chemokine receptor for mediating immune homeostasis, however, the role of CCR4 in colorectal cancer (CRC) remains unknown. In this study, we found that high expression of CCR4 in CRC tissues was correlated with shorter overall survival and disease free survival. In vitro and in vivo experiments revealed that silencing CCR4 attenuated the invasion and metastasis of CRC cells, whereas ectopic overexpression of CCR4 contributed to the forced metastasis of these cells. We further demonstrated that matrix metalloproteinase 13 (MMP13) played an important role in CCR4-mediated cancer cell invasion, which is up-regulated by ERK/NF-κB signaling. Positive correlation between CCR4 and MMP13 expression was also observed in CRC tissues. Moreover, our investigations showed that the level of CCR4 could be induced by TNF-α dependent of NF-κB activation in CRC cells. CCR4 might be implicated in TNF-α-regulated cancer cells metastasis. Combination of CCR4 and TNF-α is a more powerful prognostic marker for CRC patients. These findings suggest that CCR4 facilitates metastasis through ERK/NF-κB/MMP13 signaling and acts as a downstream target of TNF-α. CCR4 inhibition may be a promising therapeutic option for suppressing CRC metastasis.

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CC motif chemokine ligand 19 suppressed colorectal cancer in vivo accompanied by an increase in IL-12 and IFN-γ

Cited by 16 publications

References 18 publications

CCL19 suppresses angiogenesis through promoting miR-206 and inhibiting Met/ERK/Elk-1/HIF-1α/VEGF-A pathway in colorectal cancer

CCL19 suppresses angiogenesis through promoting miR-206 and inhibiting Met/ERK/Elk-1/HIF-1α/VEGF-A pathway in colorectal cancer

Therapeutic Lymphoid Organogenesis in the Tumor Microenvironment

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

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