Tunneling nanotubes provide a unique conduit for intercellular transfer of cellular contents in human malignant pleural mesothelioma.
Tunneling nanotubes provide a unique conduit for intercellular transfer of cellular contents in human malignant pleural mesothelioma.
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DOI：
10.1371/journal.pone.0033093
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Moore MA
中科院分区：
文献类型：
--
作者：
Lou E;Fujisawa S;Morozov A;Barlas A;Romin Y;Dogan Y;Gholami S;Moreira AL;Manova-Todorova K;Moore MA
微管纳米管是长的、非粘附的基于F-肌动蛋白的细胞质延伸，其连接近端或远端细胞并促进细胞间转移。纳米管的鉴定仅限于细胞系，它们在癌症中的作用仍不清楚。我们在间皮瘤细胞系和原代人类间皮瘤细胞中检测到隧道纳米管。使用低血清、高血糖、酸性生长培养基，我们刺激了纳米管的形成和囊泡、蛋白质和线粒体在细胞之间的双向转移。值得注意的是，纳米管在恶性细胞之间或正常间皮细胞之间形成，但在恶性细胞和正常细胞之间不形成。免疫荧光染色显示其肌动蛋白为基础的组装和结构。二甲双胍和mTor抑制剂依维莫司有效地抑制了纳米管的形成。共聚焦显微镜与三维重建的切片手术标本首次证明存在纳米管在人类间皮瘤和肺腺癌肿瘤标本。我们提供了人类原发性肿瘤和癌细胞中隧道纳米管的第一个证据，并提出这些结构在癌细胞发病和侵袭中起着重要作用。
Tunneling nanotubes are long, non-adherent F-actin-based cytoplasmic extensions which connect proximal or distant cells and facilitate intercellular transfer. The identification of nanotubes has been limited to cell lines, and their role in cancer remains unclear. We detected tunneling nanotubes in mesothelioma cell lines and primary human mesothelioma cells. Using a low serum, hyperglycemic, acidic growth medium, we stimulated nanotube formation and bidirectional transfer of vesicles, proteins, and mitochondria between cells. Notably, nanotubes developed between malignant cells or between normal mesothelial cells, but not between malignant and normal cells. Immunofluorescent staining revealed their actin-based assembly and structure. Metformin and an mTor inhibitor, Everolimus, effectively suppressed nanotube formation. Confocal microscopy with 3-dimensional reconstructions of sectioned surgical specimens demonstrated for the first time the presence of nanotubes in human mesothelioma and lung adenocarcinoma tumor specimens. We provide the first evidence of tunneling nanotubes in human primary tumors and cancer cells and propose that these structures play an important role in cancer cell pathogenesis and invasion.
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影响因子：
44.1
作者：
通讯作者：
--
影响因子：
4.8
作者：
Faoro, Leonardo;Singleton, Patrick A.;Salgia, Ravi
通讯作者：
Salgia, Ravi
DOI：
10.1165/rcmb.2003-0238oc
发表时间：
2004-07-01
影响因子：
6.4
作者：
Bard, MP;Hegmans, JP;Lambrecht, BN
通讯作者：
Lambrecht, BN
影响因子：
5
作者：
Beckner, ME;Gobbel, GT;Pollack, IF
通讯作者：
Pollack, IF
影响因子：
3.2
作者：
Galkina, Svetlana I.;Stadnichuk, Vladimir I.;Klein, Thomas
通讯作者：
Klein, Thomas