體內(nèi)顯微鏡顯示，巨噬細胞極化在局部促進遷移癌細胞中微管的協(xié)調(diào)動態(tài)

中文摘要：

微管（MTs）調(diào)節(jié)有絲分裂、定向信號傳導，并且是癌癥的治療靶點。然而，在體內(nèi)分析癌細胞在腫瘤微環(huán)境中微管的行為仍然具有挑戰(zhàn)性。在這里，我們開發(fā)了一個成像流程，使用加端追蹤和活體顯微鏡來量化活體異種移植腫瘤模型中的微管動力學。在分析的特征中，體內(nèi)癌細胞沿其細胞長軸顯示出比二維體外培養(yǎng)更高的一致性微管取向，并且與三維膠原凝膠培養(yǎng)不同。這種體內(nèi)微管表型在體外與IL4極化的巨噬細胞（MΦ）共同培養(yǎng)時得以再現(xiàn)。巨噬細胞清除、微管破壞、靶向激酶抑制以及通過IL10R阻斷改變巨噬細胞極化均會降低微管一致性和/或腫瘤細胞伸長。我們顯示，微管一致性是體內(nèi)腫瘤細胞動力學和遷移的決定特征，并受到促腫瘤巨噬細胞局部信號的調(diào)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.

論文信息：

論文題目：In vivo microscopy reveals macrophage polarization locally promotes coherent microtubule dynamics in migrating cancer cells

期刊名稱：Nature Communications

時間期卷：11, Article number: 3521(2020)

在線時間：2020年7月14日

DOI： doi.org/10.1038/s41467-020-15636-8

產(chǎn)品信息：

貨號：CP-005-005

規(guī)格：5ml+5ml

品牌：Liposoma

產(chǎn)地：荷蘭

名稱：Clodronate Liposomes& Control Liposomes

辦事處：Target Technology(靶點科技)

Clodronate Liposomes氯膦酸鹽脂質(zhì)體清除腫瘤模型中TAM腫瘤相關(guān)巨噬細胞 ，荷蘭Liposoma巨噬細胞清除劑ClodronateLiposomes見刊于Nature Communications：體內(nèi)顯微鏡顯示，巨噬細胞極化在局部促進遷移癌細胞中微管的協(xié)調(diào)動態(tài)。

Liposoma巨噬細胞清除劑Clodronate Liposomes氯膦酸二鈉脂質(zhì)體清除腫瘤相關(guān)巨噬細胞的材料和方法：

Disseminated OVCA imaging

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.

材料和方法文獻截圖：