Preferential transfer of mitochondria from endothelial to cancer cells through tunneling nanotubes modulates chemoresistance.
Preferential transfer of mitochondria from endothelial to cancer cells through tunneling nanotubes modulates chemoresistance.
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DOI：
10.1186/1479-5876-11-94
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发表时间：
2013-04-10
影响因子：
7.4
通讯作者：
Rafii A
中科院分区：
文献类型：
--
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
在过去的几十年里，我们对癌症的看法发生了变化。事实上，肿瘤现在被认为是复杂的实体，其中肿瘤和基质成分密切相互作用。在肿瘤间质的不同成分中，细胞成分起着原始作用。骨髓源性间充质细胞（MSC）被吸引到肿瘤部位并支持肿瘤生长。内皮细胞（EC）在血管生成中起主要作用。虽然文献记录了基质细胞和癌细胞之间的串扰的许多方面，但直接异细胞接触的作用尚未明确确立。最近，已显示出Tuns纳米管（TnTs）支持细胞系内的质膜组分、胞质分子和细胞器的细胞到细胞的转移。在此，我们研究了基质（MSC和EC）和癌细胞之间的异质细胞TnTs的形成。我们证明了TnTs发生在不同的癌细胞，基质细胞和癌基质细胞系之间。我们发现，TnTs样结构发生在三维锚定独立的球体，也在肿瘤外植体培养。在我们的培养条件下，TnTs形成后发生大膜粘附。我们发现，细胞质内容物的细胞间转移发生在癌细胞和MSC或EC之间类似，但我们强调，线粒体的交换优先发生在内皮细胞和癌细胞之间。我们说明，获得线粒体的癌细胞表现出耐药性。我们的研究结果表明，灌注独立的作用，内皮细胞显示直接内皮细胞癌细胞线粒体交换相关的表型调制。这支持了内皮在转移性小生境的构成中的另一个作用。
Our vision of cancer has changed during the past decades. Indeed tumors are now perceived as complex entities where tumoral and stromal components interact closely. Among the different elements of tumor stroma the cellular component play a primordial role. Bone Marrow derived mesenchymal cells (MSCs) are attracted to tumor sites and support tumor growth. Endothelial cells (ECs) play a major role in angiogenesis. While the literature documents many aspects of the cross talk between stromal and cancer cells, the role of direct hetero-cellular contact is not clearly established. Recently, Tunneling nanotubes (TnTs) have been shown to support cell-to-cell transfers of plasma membrane components, cytosolic molecules and organelles within cell lines. Herein, we have investigated the formation of heterocellular TnTs between stromal (MSCs and ECs) and cancer cells. We demonstrate that TnTs occur between different cancer cells, stromal cells and cancer-stromal cell lines. We showed that TnTs-like structure occurred in 3D anchorage independent spheroids and also in tumor explant cultures. In our culture condition, TnTs formation occurred after large membrane adhesion. We showed that intercellular transfers of cytoplasmic content occurred similarly between cancer cells and MSCs or ECs, but we highlighted that the exchange of mitochondria occurred preferentially between endothelial cells and cancer cells. We illustrated that the cancer cells acquiring mitochondria displayed chemoresistance. Our results illustrate the perfusion-independent role of the endothelium by showing a direct endothelial to cancer cell mitochondrial exchange associated to phenotypic modulation. This supports another role of the endothelium in the constitution of the metastatic niche.
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影响因子：
2.3
作者：
Gurke, Steffen;Barroso, Joao F. V.;Gerdes, Hans-Hermann
通讯作者：
Gerdes, Hans-Hermann
影响因子：
--
作者：
Lou E;Fujisawa S;Barlas A;Romin Y;Manova-Todorova K;Moore MA;Subramanian S
通讯作者：
Subramanian S
影响因子：
7.5
作者：
Gerdes, Hans-Hermann;Carvalho, Raquel Negrao
通讯作者：
Carvalho, Raquel Negrao
影响因子：
44.1
作者：
通讯作者：
--
影响因子：
3.7
作者：
Lou E;Fujisawa S;Morozov A;Barlas A;Romin Y;Dogan Y;Gholami S;Moreira AL;Manova-Todorova K;Moore MA
通讯作者：
Moore MA