CCL3-CCR5 axis contributes to progression of esophageal squamous cell carcinoma by promoting cell migration and invasion via Akt and ERK pathways.
Aged
Carcinoma, Squamous Cell
/ genetics
Cell Line, Tumor
Cell Movement
/ genetics
Chemokine CCL3
/ genetics
Disease Progression
Esophageal Neoplasms
/ genetics
Female
Gene Expression Profiling
/ methods
Gene Expression Regulation, Neoplastic
Humans
Kaplan-Meier Estimate
MAP Kinase Signaling System
/ genetics
Macrophages
/ metabolism
Male
Middle Aged
Monocytes
/ metabolism
Neoplasm Invasiveness
Proto-Oncogene Proteins c-akt
/ genetics
Receptors, CCR5
/ genetics
Journal
Laboratory investigation; a journal of technical methods and pathology
ISSN: 1530-0307
Titre abrégé: Lab Invest
Pays: United States
ID NLM: 0376617
Informations de publication
Date de publication:
09 2020
09 2020
Historique:
received:
09
12
2019
accepted:
08
05
2020
revised:
08
05
2020
pubmed:
28
5
2020
medline:
24
11
2020
entrez:
28
5
2020
Statut:
ppublish
Résumé
Tumor-associated macrophages (TAMs) contribute to the progression and mortality of various malignancies. We reported that high numbers of infiltrating TAMs were significantly associated with tumor progression and poor prognosis in esophageal squamous cell carcinoma (ESCC). In our previous investigation of TAMs' actions in ESCC, we compared gene expression profiles between peripheral blood monocyte (PBMo)-derived macrophages and TAM-like macrophages stimulated with conditioned media of ESCC cell lines. Among the upregulated genes in the TAM-like macrophages, we focused on CC chemokine ligand 3 (CCL3), which was reported to contribute to tumor progression in several malignancies. Herein, we observed that not only TAMs but also ESCC cell lines expressed CCL3. A CCL3 receptor, CC chemokine receptor 5 (CCR5) was expressed in the ESCC cell lines. Treating the ESCC cell lines with recombinant human (rh)CCL3 induced the phosphorylations of Akt and ERK, which were suppressed by CCR5 knockdown. Migration and invasion of ESCC cells were promoted by treatment with rhCCL3 and co-culture with TAMs. TAMs/rhCCL3-promoted cell migration and invasion were suppressed by inhibition of the CCL3-CCR5 axis, PI3K/Akt, and MEK/ERK pathways. Treatment with rhCCL3 upregulated MMP2 and VEGFA expressions in ESCC cell lines. Our immunohistochemical analysis of 68 resected ESCC cases showed that high expression of CCL3 and/or CCR5 in ESCC tissues was associated with poor prognosis. High CCR5 expression was associated with deeper invasion, presence of vascular invasion, higher pathological stage, higher numbers of infiltrating CD204
Identifiants
pubmed: 32457351
doi: 10.1038/s41374-020-0441-4
pii: S0023-6837(22)00360-9
pmc: PMC7438203
doi:
Substances chimiques
Chemokine CCL3
0
Receptors, CCR5
0
Proto-Oncogene Proteins c-akt
EC 2.7.11.1
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
1140-1157Références
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