HMGB1 attenuates anti-metastatic defence of the liver in colorectal cancer

作者：Luo Yi; Ohmori Hitoshi; Fujii Kiyomu; Moriwaka Yukiko; Sasahira Tomonori; Kurihara Miyako; Tatsumoto Naokuni; Sasaki Takamitsu; Yamashita Yuichi; Kuniyasu Hiroki^*

来源：European Journal of Cancer, 2010, 46(4): 791-799.

DOI：10.1016/j.ejca.2009.11.011

• Colorectal cancer
• Liver metastasis
• HMGB1
• Kupffer cell

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.

• 出版日期2010-3