Identification and Characterization of Tunneling Nanotubes Involved in Human Mast Cell FcεRI-Mediated Apoptosis of Cancer Cells.
Identification and Characterization of Tunneling Nanotubes Involved in Human Mast Cell FcεRI-Mediated Apoptosis of Cancer Cells.
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作者：
肥大细胞（MCs）普遍存在于大多数组织以及肿瘤内部和周围。它们在癌症发病机制中的作用仍然是一个开放的研究领域，它们与肿瘤细胞的相互作用尚未被探索。本文描述了一种涉及隧道纳米管（TnT）和其他膜结构的人类MCs与肿瘤细胞之间通信的新机制。这些通讯结构的形成依赖于MC受体通过肿瘤特异性免疫球蛋白与肿瘤抗原相互作用，并导致MC的肿瘤杀伤介质进入肿瘤细胞。MC杀伤肿瘤细胞的这一机制对理解肿瘤的发病机制具有重要意义。肥大细胞（MCs）几乎存在于所有组织中，它们参与先天和适应性免疫反应。它们也存在于肿瘤内部和肿瘤周围，但它们与癌细胞的相互作用以及对癌细胞生长和转移的影响尚不清楚。在这项研究中，我们研究了ige - fc - ε - ri介导的人脂肪源性肥大细胞（ADMC）和癌细胞之间细胞间通讯的新机制。利用显微镜和多种分子特异性指示染料，研究了MCs和肿瘤细胞之间异型隧道纳米管（TnT）和膜结构的形成。我们发现一些mc特异性结构依赖于人类肿瘤ige致敏的mc与肿瘤细胞表面抗原之间的特异性相互作用。TnT、膜泡和其他MC特异性结构的形成与fcε ri脱粒平行，发生时间为30分钟，持续时间长达24小时。fcε ri激活的MCs对肿瘤细胞的TnT特异性粘附的特征是MC颗粒含量转运到肿瘤细胞中，包括胰蛋白酶和TNF-α。这种相互作用导致肿瘤细胞凋亡，这与以往在癌症微环境中检查组织细胞的研究不同。异型TnT的形成导致侵袭性肿瘤细胞表型的刺激，增加肿瘤细胞的侵袭性和癌细胞的化疗耐药。这些研究描述了ige介导的相互作用和fcε ri激活的mc介导的通过形成TnT杀伤肿瘤细胞的迄今未被认识的机制。
Mast cells (MCs) are ubiquitously found in most tissues and in and around tumors. Their role in cancer pathogenesis remains an open area of investigation, and their interactions with tumor cells has not been explored. Here, a novel mechanism of communication between human MCs and tumor cells involving tunneling nanotubes (TnT) and other membrane structures is described. The formation of these communication structures is dependent on MC receptors interacting with tumor antigens through tumor-specific immunoglobulins and results in tumor-killing mediators from MC entering the tumor cells. This mechanism underlying the MC killing of tumor cells has important implications in understanding cancer pathogenesis. Mast cells (MCs) are found in practically all tissues where they participate in innate and adaptive immune responses. They are also found in and around tumors, yet their interactions with cancer cells and the resulting impact on cancer cell growth and metastasis are not well understood. In this study, we examined a novel mechanism of IgE-FcεRI-mediated, intercellular communication between human adipose-derived mast cells (ADMC) and cancer cells. The formation of heterotypic tunneling nanotubes (TnT) and membrane structures between MCs and tumor cells in vitro was examined using microscopy and a diverse array of molecule-specific indicator dyes. We show that several MC-specific structures are dependent on the specific interactions between human tumor IgE-sensitized MCs and antigens on the tumor cell surface. The formation of TnT, membrane blebs and other MC-specific structures paralleled FcεRI-degranulation occurring within 30 min and persisting for up to 24 h. The TnT-specific adhesion of FcεRI-activated MCs to tumor cells was characterized by the transport of the MC granule content into the tumor cells, including tryptase and TNF-α. This interaction led to apoptosis of the tumor cells, which differs from previous studies examining tissue cells within the cancer microenvironment. The formation of heterotypic TnT results in stimulation of an invasive tumor cell phenotype and increased tumor cell invasion and chemoresistance of the cancer cells. These studies describe a heretofore-unrecognized mechanism underlying IgE-mediated interactions and FcεRI-activated MC-mediated killing of tumor cells through the formation of TnT.
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影响因子：
15.9
作者：
Blair, RJ;Meng, H;Gruber, BL
通讯作者：
Gruber, BL
影响因子：
64.8
作者：
GORDON, JR;GALLI, SJ
通讯作者：
GALLI, SJ
影响因子：
5.8
作者：
Teo, Pearline Zhaoying;Utz, Paul J.;Mollick, Joseph A.
通讯作者：
Mollick, Joseph A.
影响因子：
7.4
作者：
Pasquier J;Guerrouahen BS;Al Thawadi H;Ghiabi P;Maleki M;Abu-Kaoud N;Jacob A;Mirshahi M;Galas L;Rafii S;Le Foll F;Rafii A
通讯作者：
Rafii A
人肿瘤针对细胞毒性肥大细胞进行癌症免疫疗法。
影响因子：
4.7
作者：
Fereydouni, Mohammad;Ahani, Elnaz;Desai, Parth;Motaghed, Mona;Dellinger, Anthony;Metcalfe, Dean D.;Yin, Yuzhi;Lee, Sung Hyun;Kafri, Tal;Bhatt, Aadra P.;Dellinger, Kristen;Kepley, Christopher L.
通讯作者：
Kepley, Christopher L.