中文摘要：
复发性乳腺癌通常会对标准护理疗法产生耐药性。确定导致癌症复发的可靶向因素仍然是改善长期结果的限速步骤。在这项研究中，我们确定肿瘤细胞来源的骨桥蛋白是肿瘤复发的自分泌和旁分泌驱动因素。骨桥蛋白促进肿瘤细胞增殖，募集巨噬细胞，并与 IL-4 协同作用，使它们进一步极化为促肿瘤状态。氯膦酸盐脂质体（Liposoma）清除/耗竭巨噬细胞和抑制骨桥蛋白可减少复发性肿瘤生长。此外，在原代荷瘤雌性小鼠中靶向骨桥蛋白可防止转移，允许 T 细胞浸润和激活，并改善抗 PD-1 免疫治疗反应。临床上，骨桥蛋白在复发性转移性肿瘤中的表达高于女性患者匹配的原发性乳腺肿瘤。骨桥蛋白与巨噬细胞浸润呈正相关，随着肿瘤分级的升高而增加，其通路活性升高与预后不良和长期复发相关。我们的研究结果表明了临床意义和基于骨桥蛋白在乳腺癌进展和复发中的多轴作用的替代治疗策略。
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.
论文信息：
论文题目：Osteopontin is a therapeutic target that drives breast cancer recurrence
期刊名称：Nature Communications
时间期卷：15, Article number: 9174 (2024)
在线时间：2024年10月24日
DOI：doi.org/10.1038/s41467-024-53023-9
产品信息：
货号：CP-005-005
规格：5ml+5ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes and Control Liposomes
办事处：Target Technology（靶点科技）
Clodronate Liposomes氯膦酸盐脂质体助力乳腺癌模型研究，荷兰Liposoma巨噬细胞清除剂Clodronate Liposomes见刊于Nature Communications：骨桥蛋白（osteopontin，OPN）是驱动乳腺癌复发的治疗靶点
氯膦酸二钠脂质体清除巨噬细胞助力乳腺癌瘤模型肿瘤免疫研究
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体的材料和方法：
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.
