中文摘要：

腸道菌群與結(jié)直腸癌（CRC）的發(fā)生發(fā)展密切相關(guān)。本研究發(fā)現(xiàn)，H. hathewayi——一種此前被報(bào)道與CRC相關(guān)的共生菌——在自發(fā)性CRC模型中反而對腸道腫瘤生長和腸道菌群失調(diào)具有保護(hù)作用。H. hathewayi可減緩?fù)N異體移植結(jié)腸癌細(xì)胞的生長，并抑制ApcMin/+ 小鼠的CRC進(jìn)展，同時(shí)伴隨瘤內(nèi) CD14b+ 腫瘤相關(guān)巨噬細(xì)胞（TAMs）增多。這種保護(hù)效應(yīng)歸因于 H. hathewayi 分泌至 Hh.CM 中的蛋白，我們鑒定出一種含細(xì)胞壁結(jié)合重復(fù)序列的蛋白（CWBR-CP）是關(guān)鍵功能介質(zhì)。CWBR-CP 在多種小鼠模型中重現(xiàn)了 H. hathewayi 的抑瘤效果，并誘導(dǎo)巨噬細(xì)胞向 M1 樣極化轉(zhuǎn)變。機(jī)制上，CWBR-CP 直接結(jié)合激肽釋放酶 8（KLK8）并下調(diào)其在巨噬細(xì)胞中的表達(dá)。KLK8 的下調(diào)進(jìn)而激活緩激肽受體 B1（B1R），觸發(fā) PI3K/AKT/NF-κB 通路，最終促進(jìn) M1 型巨噬細(xì)胞極化。

英文摘要：

Gut microbiota has been widely implicated in colorectal cancer (CRC). Here, we show that H. hathewayi, a commensal bacterium previously associated with CRC, is protective against intestinal tumor growth, and gut dysbiosis in a spontaneous CRC model. H. hathewayi attenuated the growth of allografted colon carcinoma cells and suppressed CRC progression in ApcMin/+ mice, concomitant with an increased intratumoral CD14b+ tumor-associated macrophages (TAMs). Such protective effect was attributed to H. hathewayi-secreted proteins from Hh.CM, and we identified a cell wall-binding repeat-containing protein (CWBR-CP) as the key functional mediator. CWBR-CP recapitulated the tumor suppression of H. hathewayi in multiple mouse models and induced a corresponding shift toward M1-like macrophage polarization. Mechanistically, CWBR-CP directly bound to kallikrein 8 (KLK8) and downregulated its expression in macrophages. KLK8 downregulation, in turn, activated bradykinin receptor B1 (B1R), triggering the PI3K/AKT/NF-κB pathway and ultimately promoting M1 macrophage polarization.

論文信息：

論文題目：A secreted protein from Hungatella hathewayi inhibits colorectal cancer by reprogramming intratumoral CD14b+ macrophages

期刊名稱：Cell Reports

時(shí)間期卷：Volume 45, Issue 9, 117988

Doi：10.1016/j.celrep.2026.117988

產(chǎn)品信息：

貨號：CP-010-010

規(guī)格：10ml+10ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes&Control Liposomes

辦事處：靶點(diǎn)科技

Clodronate Liposomes氯膦酸鹽脂質(zhì)體清除APC-Min 小鼠巨噬細(xì)胞，APC-Min 小鼠是攜帶 Apc 基因多發(fā)性腸道腫瘤（Min）突變的雜合小鼠。純合小鼠會致死。 這種小鼠能自發(fā)產(chǎn)生 腸道腺瘤，并在生存、生長、攝食量和 腸道病變 等方面表現(xiàn)出 腸癌疾病 的特征。 因此，APC-Min 小鼠可用于研究家族性腺瘤息肉病（FAP）、結(jié)直腸癌等腫瘤或腫瘤相關(guān)疾病，以及 Wnt/β-catenin 信號通路的調(diào)控機(jī)制。荷蘭Liposoma巨噬細(xì)胞清除劑ClodronateLiposomes見刊于Cell Reports：一種源自 Hungatella hathewayi 的分泌蛋白通過重編程瘤內(nèi)CD14b+巨噬細(xì)胞抑制結(jié)直腸癌。

Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體清除巨噬細(xì)胞的材料和方法：

In vivo macrophage depletion

For the macrophage depletion model, male ApcMin/+ mice were orally gavaged with an oral administration of live H. hathewayi (1.0 × 108 CFU per mouse) in 0.1 mL sterile saline containing 2.5% glycerol for 9 weeks (n = 6). During this process, the mice were injected (i.p) with PBS liposomes and clodronate liposomes (LIPOSOMA) every two weeks and body weight and bleeding score were assessed daily.

巨噬細(xì)胞清除材料和方法文獻(xiàn)截圖：