中文摘要：
微管（MTs）调节有丝分裂、定向信号传导，并且是癌症的治疗靶点。然而，在体内分析癌细胞在肿瘤微环境中微管的行为仍然具有挑战性。在这里，我们开发了一个成像流程，使用加端追踪和活体显微镜来量化活体异种移植肿瘤模型中的微管动力学。在分析的特征中，体内癌细胞沿其细胞长轴显示出比二维体外培养更高的一致性微管取向，并且与三维胶原凝胶培养不同。这种体内微管表型在体外与IL4极化的巨噬细胞（MΦ）共同培养时得以再现。巨噬细胞清除、微管破坏、靶向激酶抑制以及通过IL10R阻断改变巨噬细胞极化均会降低微管一致性和/或肿瘤细胞伸长。我们显示，微管一致性是体内肿瘤细胞动力学和迁移的决定特征，并受到促肿瘤巨噬细胞局部信号的调控。
英文摘要：
Microtubules (MTs) mediate mitosis, directional signaling, and are therapeutic targets in cancer. Yet in vivo analysis of cancer cell MT behavior within the tumor microenvironment remains challenging. Here we developed an imaging pipeline using plus-end tip tracking and intravital microscopy to quantify MT dynamics in live xenograft tumor models. Among analyzed features, cancer cells in vivo displayed higher coherent orientation of MT dynamics along their cell major axes compared with 2D in vitro cultures, and distinct from 3D collagen gel cultures. This in vivo MT phenotype was reproduced in vitro when cells were co-cultured with IL4-polarized MΦ. MΦ depletion, MT disruption, targeted kinase inhibition, and altered MΦ polarization via IL10R blockade all reduced MT coherence and/or tumor cell elongation. We show that MT coherence is a defining feature for in vivo tumor cell dynamics and migration, modulated by local signaling from pro-tumor macrophages.
论文信息：
论文题目：In vivo microscopy reveals macrophage polarization locally promotes coherent microtubule dynamics in migrating cancer cells
期刊名称：Nature Communications
时间期卷：11, Article number: 3521(2020)
在线时间：2020年7月14日
DOI： doi.org/10.1038/s41467-020-15636-8
产品信息：
货号：CP-005-005
规格：5ml+5ml
品牌：Liposoma
产地：荷兰
名称：Clodronate Liposomes& Control Liposomes
办事处：Target Technology(靶点科技)
Clodronate Liposomes氯膦酸盐脂质体清除肿瘤模型中TAM肿瘤相关巨噬细胞 ，荷兰Liposoma巨噬细胞清除剂ClodronateLiposomes见刊于Nature Communications：体内显微镜显示，巨噬细胞极化在局部促进迁移癌细胞中微管的协调动态。
Liposoma巨噬细胞清除剂Clodronate Liposomes氯膦酸二钠脂质体清除肿瘤相关巨噬细胞的材料和方法：
Five million ES2 cells stably transduced to express the GFP-variant, mClover, were suspended in 200 μL PBS and i.p. injected into female nu/nu mice of 6–10 weeks age to establish a model of disseminated OVCA. Beginning 3 days after tumor inoculation, mice were treated i.p. with 150 μL clod-lip (5 mg mL−1) or PBS control liposomes (Liposoma BV). Three and 6 days after, 50 μL clod-lip or PBS-lip were again used. The following day, PacBlue-labeled polyglucose NPs (Macrin) were administered i.v. and 24 h later, mice were sacrificed for immediate ex vivo confocal imaging of tumor-bearing organs. Macrin has been shown by flow cytometry and imaging to be >90% selective for TAMs in mice.
材料和方法文献截图：
