Activated macrophages promote invasion by early colorectal cancer via an interleukin 1β-serum amyloid A1 axis.
Activated macrophages promote invasion by early colorectal cancer via an interleukin 1β-serum amyloid A1 axis.
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DOI：
10.1111/cas.15080
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发表时间：
2021-10
期刊：
影响因子：
5.7
通讯作者：
Suzuki H
中科院分区：
文献类型：
--
作者：
Sudo G;Aoki H;Yamamoto E;Takasawa A;Niinuma T;Yoshido A;Kitajima H;Yorozu A;Kubo T;Harada T;Ishiguro K;Kai M;Katanuma A;Yamano HO;Osanai M;Nakase H;Suzuki H
黏膜下浸润和淋巴结转移是影响早期结直肠癌（CRC）治疗选择的重要问题。在本研究中，我们旨在揭示早期crc侵袭性的分子机制。我们对从T1 CRC组织中分离的低分化成分（PORs）及其正常对应物进行了RNA‐测序（RNA‐seq），并检测到PORs中血清淀粉样蛋白A1 （SAA1）的显著上调。免疫组化分析显示SAA1在T1b crc侵袭前的PORs中特异性表达。CRC细胞中SAA1的上调促进了细胞的迁移和侵袭。用结直肠癌细胞系和THP‐1细胞共培养实验表明，巨噬细胞产生的白细胞介素1β （IL‐1β）可诱导结直肠癌细胞中SAA1的表达。阻断IL‐1β可抑制巨噬细胞诱导SAA1和促进结直肠癌细胞迁移和侵袭。这些发现得到了原发T1 crc免疫组织化学分析的支持，显示在SAA1阳性侵袭前区有M1样/M2样巨噬细胞的积累。此外，CRC细胞产生的SAA1刺激巨噬细胞中基质金属蛋白酶- 9的上调。我们的数据表明，早期crc侵袭前沿的肿瘤相关巨噬细胞通过诱导SAA1促进癌细胞迁移和侵袭，SAA1可能是一种预测性生物标志物和有用的治疗靶点。我们发现血清淀粉样蛋白A1 （SAA1）在T1期结直肠癌（CRC）侵袭前的低分化区域上调。我们发现肿瘤相关的巨噬细胞在侵袭前积聚，通过白细胞介素1β刺激结直肠癌细胞SAA1上调，促进结直肠癌细胞迁移和侵袭。我们还发现CRC细胞分泌的SAA1刺激侵袭前巨噬细胞中基质金属蛋白酶- 9的上调。
Submucosal invasion and lymph node metastasis are important issues affecting treatment options for early colorectal cancer (CRC). In this study, we aimed to unravel the molecular mechanism underlying the invasiveness of early CRCs. We performed RNA‐sequencing (RNA‐seq) with poorly differentiated components (PORs) and their normal counterparts isolated from T1 CRC tissues and detected significant upregulation of serum amyloid A1 (SAA1) in PORs. Immunohistochemical analysis revealed that SAA1 was specifically expressed in PORs at the invasive front of T1b CRCs. Upregulation of SAA1 in CRC cells promoted cell migration and invasion. Coculture experiments using CRC cell lines and THP‐1 cells suggested that interleukin 1β (IL‐1β) produced by macrophages induces SAA1 expression in CRC cells. Induction of SAA1 and promotion of CRC cell migration and invasion by macrophages were inhibited by blocking IL‐1β. These findings were supported by immunohistochemical analysis of primary T1 CRCs showing accumulation of M1‐like/M2‐like macrophages at SAA1‐positive invasive front regions. Moreover, SAA1 produced by CRC cells stimulated upregulation of matrix metalloproteinase‐9 in macrophages. Our data suggest that tumor‐associated macrophages at the invasive front of early CRCs promote cancer cell migration and invasion through induction of SAA1 and that SAA1 may be a predictive biomarker and a useful therapeutic target. We identified that serum amyloid A1 (SAA1) is upregulated in the poorly differentiated regions at the invasive front of T1 stage colorectal cancer (CRC). We found that tumor‐associated macrophages accumulated at the invasive front, where they stimulated SAA1 upregulation in CRC cells via interleukin 1β and promoted CRC cell migration and invasion. We also show that SAA1 secreted by CRC cells stimulates matrix metalloproteinase‐9 upregulation in macrophages at the invasive front.
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影响因子：
8
作者：
Hansen, M. T.;Forst, B.;Grigorian, M.
通讯作者：
Grigorian, M.
DOI：
10.1158/1078-0432.ccr-18-1033
发表时间：
2019-01-15
期刊：
Clinical cancer research : an official journal of the American Association for Cancer Research
影响因子：
--
作者：
Lee LYW;Woolley C;Starkey T;Biswas S;Mirshahi T;Bardella C;Segditsas S;Irshad S;Tomlinson I
通讯作者：
Tomlinson I
影响因子：
5.7
作者：
Arima K;Komohara Y;Bu L;Tsukamoto M;Itoyama R;Miyake K;Uchihara T;Ogata Y;Nakagawa S;Okabe H;Imai K;Hashimoto D;Chikamoto A;Yamashita YI;Baba H;Ishimoto T
通讯作者：
Ishimoto T
影响因子：
13
作者：
De Buck M;Gouwy M;Wang JM;Van Snick J;Proost P;Struyf S;Van Damme J
通讯作者：
Van Damme J
DOI：
10.1016/j.bbrc.2005.03.069
发表时间：
2005-05-13
影响因子：
3.1
作者：
Lee, HY;Kim, MK;Bae, YS
通讯作者：
Bae, YS