中文摘要：

復發性乳腺癌通常會對標準護理療法產生耐藥性。確定導致癌癥復發的可靶向因素仍然是改善長期結果的限速步驟。在這項研究中，我們確定腫瘤細胞來源的骨橋蛋白是腫瘤復發的自分泌和旁分泌驅動因素。骨橋蛋白促進腫瘤細胞增殖，募集巨噬細胞，并與 IL-4 協同作用，使它們進一步極化為促腫瘤狀態。氯膦酸鹽脂質體（Liposoma）清除/耗竭巨噬細胞和抑制骨橋蛋白可減少復發性腫瘤生長。此外，在原代荷瘤雌性小鼠中靶向骨橋蛋白可防止轉移，允許 T 細胞浸潤和激活，并改善抗 PD-1 免疫治療反應。臨床上，骨橋蛋白在復發性轉移性腫瘤中的表達高于女性患者匹配的原發性乳腺腫瘤。骨橋蛋白與巨噬細胞浸潤呈正相關，隨著腫瘤分級的升高而增加，其通路活性升高與預后不良和長期復發相關。我們的研究結果表明了臨床意義和基于骨橋蛋白在乳腺癌進展和復發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

時間期卷：15, Article number: 9174 (2024)

在線時間：2024年10月24日

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

產品信息：

貨號：CP-005-005

規格：5ml+5ml

品牌：Liposoma

產地：荷蘭

名稱：Clodronate Liposomes and Control Liposomes

辦事處：Target Technology（靶點科技）

Clodronate Liposomes氯膦酸鹽脂質體助力乳腺癌模型研究，荷蘭Liposoma巨噬細胞清除劑Clodronate Liposomes見刊于Nature Communications：骨橋蛋白（osteopontin，OPN）是驅動乳腺癌復發的治療靶點

氯膦酸二鈉脂質體清除巨噬細胞助力乳腺癌瘤模型腫瘤免疫研究

Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質體的材料和方法：

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.