Lung adenocarcinoma cells floating in lymphatic vessels resist anoikis by expressing phosphorylated Src
Lung adenocarcinoma cells floating in lymphatic vessels resist anoikis by expressing phosphorylated Src
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DOI：
10.1002/path.2676
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发表时间：
2010-04-01
影响因子：
7.3
通讯作者：
Miyagi, Yohei
中科院分区：
文献类型：
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作者：
Sakuma, Yuji;Takeuchi, Tomoyo;Miyagi, Yohei
抗肿瘤的能力是癌细胞转移的关键。尽管一些肺腺癌细胞系被证明通过Src的激活来抑制anoikis，但Src是否在肺腺癌组织中对anoikis的耐药性中起关键作用仍不清楚。我们检测了20个有淋巴渗透的人肺腺癌组织和9个细胞系，以研究作为anoikis耐药体内模型的组织淋巴内漂浮癌细胞是否真的抑制anoikis，以及悬浮培养的anoikis耐药体外模型的细胞系是否通过Src激活存活。我们观察到淋巴内癌细胞紧密聚集形成表达E-cadherin和磷酸化Src （p-Src）的巢。在所有组织中，这些细胞的凋亡指数与细胞外基质黏附细胞相当，表明淋巴内细胞实际上逃避了疾病。接下来，我们发现悬浮中的9个细胞系松散聚集（5个细胞系）或紧密聚集（4个细胞系），并且所有细胞都抵抗anoikis。分离后，4个细胞系（LC-KJ、HCC827、H1650和H1975）形成紧凑的球体，表达E-cadherin和p-Src。球体与淋巴内肿瘤巢相似，因此被认为是巢的合适模型。Src/Abl/Kit抑制剂PP1或Src/Abl抑制剂博舒替尼处理后，四种细胞系的球体发生凋亡。另一方面，Abl/Kit抑制剂伊马替尼不影响四种类型球体的细胞生长或凋亡。这些结果表明，Src，而不是Abl或Kit，在肺腺癌耐药的发展中起重要作用。版权所有(C) 2009大不列颠和爱尔兰病理学会。约翰·威利父子有限公司出版。
The ability to resist anoikis is critical for carcinoma cells to metastasize. Although several lung adenocarcinoma cell lines were shown to repress anoikis through the activation of Src, it remains unknown whether Src actually plays a crucial role in anoikis resistance in lung adenocarcinoma tissues. We examined 20 human lung adenocarcinoma tissues with lymphatic permeation and nine cell lines to investigate whether intralymphatic floating carcinoma cells in the tissues, used as an in vivo model of anoikis resistance, actually suppressed anoikis and whether cell lines in suspension culture, an in vitro model of anoikis resistance, survived through Src activation. We observed that the intralymphatic carcinoma cells aggregated tightly to form nests expressing E-cadherin and phosphorylated Src (p-Src). The apoptotic indices of these cells were comparable to those of extracellular matrix adhesive cells in all tissues, indicating that the intralymphatic cells actually evaded anoikis. Next, we found that the nine cell lines in suspension aggregated loosely (five cell lines) or tightly (four cell lines), and all cells resisted anoikis. Upon detachment, four cell lines (LC-KJ, HCC827, H1650, and H1975) formed compact spheroids that expressed E-cadherin and p-Src. The spheroids were similar to intralymphatic tumour nests and were thus considered to be a suitable model of the nests. The spheroids of the four cell lines underwent apoptosis after treatment with the Src/Abl/Kit inhibitor PP1 or Src/Abl inhibitor bosutinib. On the other hand, the Abl/Kit inhibitor imatinib did not affect cell growth or apoptosis in the four types of spheroids. These results indicate that Src, but not Abl or Kit, plays an essential role in the development of anoikis resistance in lung adenocarcinomas. Copyright (C) 2009 Pathological Society of Great Britain and Ireland. Published by John Wiley & Sons, Ltd.