| Literature DB >> 20018503 |
Yi Luo1, Hitoshi Ohmori, Kiyomu Fujii, Yukiko Moriwaka, Tomonori Sasahira, Miyako Kurihara, Naokuni Tatsumoto, Takamitsu Sasaki, Yuichi Yamashita, Hiroki Kuniyasu.
Abstract
High mobility group box (HMGB) 1 induces apoptosis of monocyte-lineage cells. We examined the effect of HMGB1 on Kupffer cells (KCs). In 50 Dukes C and 12 liver-metastasised Dukes D colorectal cancers (CRCs), higher HMGB1 concentration in the primary tumours and metastatic foci, and fewer KCs were found in Dukes D cases than in Dukes C cases. The portal blood HMGB1 concentration was higher in Dukes D cases than in Dukes C cases. HMGB1 induced growth inhibition and apoptosis in mouse KCs in a dose-dependent manner, which was associated with the phosphorylation of c-Jun N-terminal kinase (JNK). JNK inhibition and knockdown of HMGB1 receptor abrogated growth inhibition and apoptosis. In a nude mouse liver metastasis model, the caecal administration of HMGB1 decreased the number of KCs and increased the embedment of Colo320 CRC cells in a dose-dependent manner. HMGB1 transfection increased the liver metastasis of Colo320 cells, and the metastasis was inhibited by anti-HMGB1 antibody administration. These results suggest that HMGB1 secreted from primary tumours decreases the number of KCs and attenuates the anti-metastatic defence of the liver in patients with CRCs. Copyright 2009 Elsevier Ltd. All rights reserved.Entities:
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Year: 2009 PMID： 20018503 DOI： 10.1016/j.ejca.2009.11.011
Source DB: PubMed Journal: Eur J Cancer ISSN： 0959-8049 Impact factor: 9.162