骨橋蛋白（osteopontin，OPN）是驅(qū)動(dòng)乳腺癌復(fù)發(fā)的治療靶點(diǎn)

中文摘要：

復(fù)發(fā)性乳腺癌通常會(huì)對(duì)標(biāo)準(zhǔn)護(hù)理療法產(chǎn)生耐藥性。確定導(dǎo)致癌癥復(fù)發(fā)的可靶向因素仍然是改善長(zhǎng)期結(jié)果的限速步驟。在這項(xiàng)研究中，我們確定腫瘤細(xì)胞來(lái)源的骨橋蛋白是腫瘤復(fù)發(fā)的自分泌和旁分泌驅(qū)動(dòng)因素。骨橋蛋白促進(jìn)腫瘤細(xì)胞增殖，募集巨噬細(xì)胞，并與 IL-4 協(xié)同作用，使它們進(jìn)一步極化為促腫瘤狀態(tài)。氯膦酸鹽脂質(zhì)體（Liposoma）清除/耗竭巨噬細(xì)胞和抑制骨橋蛋白可減少?gòu)?fù)發(fā)性腫瘤生長(zhǎng)。此外，在原代荷瘤雌性小鼠中靶向骨橋蛋白可防止轉(zhuǎn)移，允許 T 細(xì)胞浸潤(rùn)和激活，并改善抗 PD-1 免疫治療反應(yīng)。臨床上，骨橋蛋白在復(fù)發(fā)性轉(zhuǎn)移性腫瘤中的表達(dá)高于女性患者匹配的原發(fā)性乳腺腫瘤。骨橋蛋白與巨噬細(xì)胞浸潤(rùn)呈正相關(guān)，隨著腫瘤分級(jí)的升高而增加，其通路活性升高與預(yù)后不良和長(zhǎng)期復(fù)發(fā)相關(guān)。我們的研究結(jié)果表明了臨床意義和基于骨橋蛋白在乳腺癌進(jìn)展和復(fù)發(fā)中的多軸作用的替代治療策略。

英文摘要：

Recurrent breast cancers often develop resistance to standard-of-care therapies. Identifying targetable factors contributing to cancer recurrence remains the rate-limiting step in improving long-term outcomes. In this study, we identify tumor cell-derived osteopontin as an autocrine and paracrine driver of tumor recurrence. Osteopontin promotes tumor cell proliferation, recruits macrophages, and synergizes with IL-4 to further polarize them into a pro-tumorigenic state. Macrophage depletion and osteopontin inhibition decrease recurrent tumor growth. Furthermore, targeting osteopontin in primary tumor-bearing female mice prevents metastasis, permits T cell infiltration and activation, and improves anti-PD-1 immunotherapy response. Clinically, osteopontin expression is higher in recurrent metastatic tumors versus female patient-matched primary breast tumors. Osteopontin positively correlates with macrophage infiltration, increases with higher tumor grade, and its elevated pathway activity is associated with poor prognosis and long-term recurrence. Our findings suggest clinical implications and an alternative therapeutic strategy based on osteopontin’s multiaxial role in breast cancer progression and recurrence.

論文信息：

論文題目：Osteopontin is a therapeutic target that drives breast cancer recurrence

期刊名稱：Nature Communications

時(shí)間期卷：15, Article number: 9174 (2024)

在線時(shí)間：2024年10月24日

DOI：doi.org/10.1038/s41467-024-53023-9

產(chǎn)品信息：

貨號(hào)：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes and Control Liposomes

辦事處：Target Technology（靶點(diǎn)科技）

Clodronate Liposomes氯膦酸鹽脂質(zhì)體助力乳腺癌模型研究，荷蘭Liposoma巨噬細(xì)胞清除劑Clodronate Liposomes見刊于Nature Communications：骨橋蛋白（osteopontin，OPN）是驅(qū)動(dòng)乳腺癌復(fù)發(fā)的治療靶點(diǎn)

氯膦酸二鈉脂質(zhì)體清除巨噬細(xì)胞助力乳腺癌瘤模型腫瘤免疫研究

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

Macrophage depletion by clodronate liposomes

MIC β1KO mice were induced until palpable “recurrent" tumors reached 50?mm3 after their primary dormancy from weekly palpations. Tumor-bearing mice were given 10?μL per gram of either PBS- or clodronate-liposomes (LIPOSOMA, Batch P03M0124 and C6M0224, respectively) three times per week through intraperitoneal injections. All mice were given 10 doses.