Chemokine (C-C Motif) Ligand 1 Derived from Tumor-Associated Macrophages Contributes to Esophageal Squamous Cell Carcinoma Progression via CCR8-Mediated Akt/Proline-Rich Akt Substrate of 40 kDa/Mammalian Target of Rapamycin Pathway
| Autor: | Mari Nishio, Masataka Fujikawa, Yu-ichiro Koma, Masayoshi Hosono, Manabu Shigeoka, Naoki Urakawa, Hiroshi Yokozaki, Masaki Shimizu, Yoshihiro Kakeji, Kohei Tanigawa, Takayuki Kodama, Hiroki Sakamoto |
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| Jazyk: | angličtina |
| Rok vydání: | 2021 |
| Předmět: |
0301 basic medicine
Chemokine Stromal cell Esophageal Neoplasms Cell CCL1 CCR8 Ligands Receptors CCR8 Pathology and Forensic Medicine 03 medical and health sciences 0302 clinical medicine Cell Movement Tumor-Associated Macrophages medicine Humans neoplasms Protein kinase B Sirolimus biology Chemistry Macrophages TOR Serine-Threonine Kinases digestive system diseases 030104 developmental biology medicine.anatomical_structure Tumor progression 030220 oncology & carcinogenesis Cancer cell Carcinoma Squamous Cell Cancer research biology.protein Esophageal Squamous Cell Carcinoma Proto-Oncogene Proteins c-akt |
| Zdroj: | American Journal of Pathology. 191(4):686-703 |
| ISSN: | 0002-9440 |
| Popis: | Tumor-associated macrophages (TAMs) promote tumor progression. The number of infiltrating TAMs is associated with poor prognosis in esophageal squamous cell carcinoma (ESCC) patients; however, the mechanism underlying this phenomenon is unclear. cDNA microarray analysis indicates that the expression of chemokine (C-C motif) ligand 1 (CCL1) is up-regulated in peripheral blood monocyte-derived macrophages stimulated using conditioned media from ESCC cells (TAM-like macrophages). Here, we evaluated the role of CCL1 in ESCC progression. CCL1 was overexpressed in TAM-like macrophages, and CCR8, a CCL1 receptor, was expressed on ESCC cell surface. TAM-like macrophages significantly enhanced the motility of ESCC cells, and neutralizing antibodies against CCL1 or CCR8 suppressed this increased motility. Recombinant human CCL1 promoted ESCC cell motility via the Akt/proline-rich Akt substrate of 40 kDa/mammalian target of rapamycin pathway. Phosphatidylinositol 3-kinase or Akt inhibitors, CCR8 silencing, and neutralizing antibody against CCR8 could significantly suppress these effects. The overexpression of CCL1 in stromal cells or CCR8 in ESCC cells was significantly associated with poor overall survival (P = 0.002 or P = 0.009, respectively) and disease-free survival (P = 0.009 or P = 0.047, respectively) in patients with ESCC. These results indicate that the interaction between stromal CCL1 and CCR8 on cancer cells promotes ESCC progression via the Akt/proline-rich Akt substrate of 40 kDa/mammalian target of rapamycin pathway, thereby providing novel therapeutic targets. |
| Databáze: | OpenAIRE |
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