Increased CCL17 serum levels are associated with improved survival in advanced melanoma

Weide, Benjamin; Allgaier, Nicolas; Hector, Andreas; Forschner, Andrea; Leiter, Ulrike; Eigentler, Thomas; Garbe, Claus; Hartl, Dominik

doi:10.1007/s00262-015-1714-4

Cited by 14 publications

(11 citation statements)

References 41 publications

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“…However, CCL17 mRNA expression was correlated with races and HER2 status, but age and stage were not found to be correlated with CCL17 expression in BC 28. Weide et al, reported that serum CCL17 level was lower in melanoma patients compared with healthy controls 29. Similar finding in our study was that of a statistically significant increase of CCL17 content in peripheral blood in BC patients compared with healthy controls, and CCL17 may therefore as differentiation maker between BC and healthy women.…”

Section: Discussionsupporting

confidence: 73%

<p>Down-regulation of CCL17 in cancer-associated fibroblasts inhibits cell migration and invasion of breast cancer through ERK1/2 pathway</p>

Chen

Yang

et al. 2019

CMAR

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Objective Cancer-associated fibroblasts (CAFs) in the tumor microenvironment are involved in cancer development and progression, including breast cancer (BC). Up-regulation of CCL17 was observed in BC and predicted a decrease in overall survival, suggesting an important role of CCL17 in BC development. Nonetheless, little is known about the role of CCL17 in the interaction between CAFs and BC. Materials and methods Real-time quantitative PCR, Western blot, and enzyme-linked immunosorbent assay were performed to examine C-C motif chemokine ligand 17 (CCL17) and C-C motif chemokine receptor 4 (CCR4) levels in BC tissues and CAFs. Cell proliferation, migration, and invasion of CAFs co-cultured with or without BC cell lines were measured by Cell Counting Kit-8 and Transwell analysis. Expression of CCL17, CCR4, dual specificity phosphatase 6 (DUSP6), matrix metallopeptidase 13 (MMP13), extracellular signal-regulated kinase (ERK) 1/2, and phosphor-ERK1/2 (p-ERK1/2) in BC cell lines co-cultured with or without CAFs was measured by Western blotting. Results We found that BC tissues and CAFs demonstrated higher levels of CCL17 compared with adjacent-normal breast tissues and adjacent-normal fibroblasts (NFs), respectively. CCL17 expression is correlated with lymph nodes, TNM stage and tumor size of BC patients. CCL17 knockdown significantly inhibited CCL17 release, CCR4 expression, and the cell proliferation of CAFs, while CCL17 overexpression demonstrated an inverse effect in NFs. Co-culture with CAFs induced the increases in cell proliferation, migration, invasion, and the expression of CCL17, CCR4, MMP13, and p-ERK1/2 in MCF-7 and MDA-MB-231 cells were markedly reversed by CCL17 knockdown in CAFs. Meanwhile, co-culture with NFs induced the malignant phenotype of MCF-7 cells was markedly enhanced by CCL17 overexpression in NFs. Moreover, DUSP6, a negative regulator of ERK1/2, was dose-dependent decrease in response to recombinant CCL17 and inhibited cell migration, invasion, MMP13 expression, and ERK1/2 activation in MCF-7 cells. Conclusion The findings of this study suggest that CCL17 may function as a novel biomarker as well as potential therapeutic target against BC and CAF-secreted CCL17 promotes BC cell migration and invasion through the DUSP6-dependent ERK1/2 pathway.

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Section: Discussionsupporting

confidence: 73%

<p>Down-regulation of CCL17 in cancer-associated fibroblasts inhibits cell migration and invasion of breast cancer through ERK1/2 pathway</p>

Chen

Yang

et al. 2019

CMAR

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“…Serum levels of C-C motif chemokine ligand 17 (CCL17) is an independent prognostic marker of distant metastasis of melanoma. Among patients with high CCL17 levels, 43% were reported to survive at 3 years [39]. Singh et al found that activation of intratumoral cluster of differentiation 40 induced T cell-mediated eradication of melanoma in the brain [40].…”

Section: Discussionmentioning

confidence: 99%

A Novel Signature of 23 Immunity-Related Gene Pairs is Prognostic of Cutaneous Melanoma

Xue

et al. 2020

SSRN Journal

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Background: We aimed to identify immune-related signature for predicting cutaneous melanoma (CM) prognosis. Methods: We used TCGA samples (n=471) to develop the best 23 Immune related gene pairs (23-IRGP) prognostic signature and divided patients into high-and low-immune risk group in TCGA dataset and validation datasets: GSE65904 (n=214), GSE59455 (n=141), and GSE22153 (n=79). Results: 23-IRGP presented precise ability in cutaneous melanoma (CM) which high-risk groups showed poor prognosis and indicated signi cant predict power in immune micro-environment and biological analysis as well. Conclusions: we established a novel promising prognostic model in CM and built the bridge between immune micro-environment and CM patient results. This approach can be applied to discover the signatures in other diseases without technical bias from different platforms.

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“…CCL17 high expression in tumor cells predicts poor survival in patients with hepatocellular carcinoma [ 24 ]. Elevated serum level of CCL17 predicts better survival in renal cell carcinoma after peptide vaccination [ 25 ] and melanoma carcinoma [ 26 ]. Researchers treated 68 subjects with IMA901, a therapeutic vaccine for RCC consisting of multiple tumor associated peptides.…”

Section: Discussionmentioning

confidence: 99%

Low CCL17 expression associates with unfavorable postoperative prognosis of patients with clear cell renal cell carcinoma

Xiong

Liu

et al. 2017

BMC Cancer

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BackgroundChemokine (C–C motif) ligand 17 (CCL17) is a chemokine mainly produced by myeloid dendritic cells. It is a ligand for CC chemokine receptor 4 (CCR4) and CC chemokine receptor 8 (CCR8). The aim of this study was to investigate prognostic values of CCL17 expression in patients with clear cell renal cell carcinoma (ccRCC).MethodsThe study included 286 patients with ccRCC. CCL17 expression was analyzed by immunohistochemistry on tissue microarrays. Prognostic values of CCL17 expression and patients’ clinical outcomes were evaluated.ResultsKaplan-Meier method showed that low CCL17 expression was associated with worse patient overall survival (OS) and recurrence-free survival (RFS) (OS, P = 0.002; RFS, P = 0.007). Low CCL17 expression was an adverse independent risk factor for OS and RFS in multivariate analyses (OS, P = 0.006, P = 0.011 for bootstrap; RFS, P = 0.002, P = 0.025 for bootstrap). We constructed two nomograms incorporating parameters derived from multivariate analyses to predict patients’ OS and RFS (OS, c-index 0.799; RFS, c-index 0.787) and they performed better than existed integrated models.ConclusionLow CCL17 expression is a potential independent adverse prognostic biomarker for recurrence and survival of patients with ccRCC after nephrectomy. Established nomograms based on this information could help predict ccRCC patients’ OS and RFS.Electronic supplementary materialThe online version of this article (doi:10.1186/s12885-017-3106-y) contains supplementary material, which is available to authorized users.

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Increased CCL17 serum levels are associated with improved survival in advanced melanoma

Cited by 14 publications

References 41 publications

<p>Down-regulation of CCL17 in cancer-associated fibroblasts inhibits cell migration and invasion of breast cancer through ERK1/2 pathway</p>

<p>Down-regulation of CCL17 in cancer-associated fibroblasts inhibits cell migration and invasion of breast cancer through ERK1/2 pathway</p>

A Novel Signature of 23 Immunity-Related Gene Pairs is Prognostic of Cutaneous Melanoma

Low CCL17 expression associates with unfavorable postoperative prognosis of patients with clear cell renal cell carcinoma

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