Open AccessTumor necrosis factor‐α induces prostate cancer cell migration in lymphatic metastasis through CCR 7 upregulation
Author(s) -
Maolake Aerken,
Izumi Kouji,
Natsagdorj Ariunbold,
Iwamoto Hiroaki,
Kadomoto Suguru,
Makino Tomoyuki,
Naito Renato,
Shigehara Kazuyoshi,
Kadono Yoshifumi,
Hiratsuka Kaoru,
Wufuer Guzailinuer,
Nastiuk Kent L.,
Mizokami Atsushi
Publication year - 2018
Publication title -
cancer science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.035
H-Index - 141
eISSN - 1349-7006
pISSN - 1347-9032
DOI - 10.1111/cas.13586
Subject(s) - prostate cancer , metastasis , tumor necrosis factor alpha , cancer research , medicine , cancer , lymph node , prostate , cancer cell , chemokine , receptor
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 ( CCR 7), whose ligand is CCL 21, 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 CCL 21/ CCR 7 axis. First, human prostate cancer cells were determined to express both TNF ‐α and CCR 7. Second, low concentrations of TNF ‐α were confirmed to induce CCR 7 in prostate cancer cells through phosphorylation of ERK . Finally, CCL 21 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 CCR 7 expression and that the CCL 21/ CCR 7 axis might increase the metastatic potential of prostate cancer cells in lymph node metastasis.