Tumor necrosis factor-α induces prostate cancer cell migration in lymphatic metastasis through CCR7 upregulation
Autor: | Aerken Maolake, Hiroaki Iwamoto, Suguru Kadomoto, Yoshifumi Kadono, Kent L. Nastiuk, Tomoyuki Makino, Kazuyoshi Shigehara, Ariunbold Natsagdorj, Atsushi Mizokami, Guzailinuer Wufuer, Kouji Izumi, Renato Naito, Kaoru Hiratsuka |
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Rok vydání: | 2017 |
Předmět: |
0301 basic medicine
Male tumor necrosis factor‐α Cancer Research Receptors CCR7 C‐C chemokine receptor type 7 MAP Kinase Signaling System C-C chemokine receptor type 7 p38 Mitogen-Activated Protein Kinases Metastasis 03 medical and health sciences Prostate cancer 0302 clinical medicine Cell Molecular and Stem Cell Biology Cell Movement Cell Line Tumor medicine Humans metastasis Lymph node Tumor microenvironment Chemokine CCL21 business.industry Tumor Necrosis Factor-alpha Cancer Prostatic Neoplasms General Medicine Original Articles lymph node medicine.disease prostate cancer Up-Regulation 030104 developmental biology medicine.anatomical_structure Oncology 030220 oncology & carcinogenesis Lymphatic Metastasis Cancer cell Cancer research Original Article Lymph business |
Zdroj: | Cancer Science |
ISSN: | 1349-7006 |
Popis: | Understanding the mechanism of lymph node metastasis, a poor prognostic sign for prostate cancer, and the further dissemination of the disease is important to develop novel treatment strategies. Recent studies have reported that C-C chemokine receptor 7 (CCR7), whose ligand is CCL21, is abundantly expressed in lymph node metastasis and promotes cancer progression. Tumor necrosis factor-α (TNF-α) is chronically produced at low levels within the tumor microenvironment. The aim of this study was to determine whether TNF-α promotes prostate cancer dissemination from metastatic lymph nodes through activation of the CCL21/CCR7 axis. First, human prostate cancer cells were determined to express both TNF-α and CCR7. Second, low concentrations of TNF-α were confirmed to induce CCR7 in prostate cancer cells through phosphorylation of ERK. Finally, CCL21 was found to promote the migration of prostate cancer cells through phosphorylation of the protein kinase p38. Our results suggest that TNF-α leads to the induction of CCR7 expression and that the CCL21/CCR7 axis might increase the metastatic potential of prostate cancer cells in lymph node metastasis. |
Databáze: | OpenAIRE |
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