Growth of lung cancer cells in three-dimensional microenvironments reveals key features of tumor malignancy.
Growth of lung cancer cells in three-dimensional microenvironments reveals key features of tumor malignancy.
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DOI：
10.1039/c1ib00090j
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发表时间：
2012-04
期刊：
影响因子：
--
通讯作者：
Radisky DC
中科院分区：
文献类型：
--
作者：
Cichon MA;Gainullin VG;Zhang Y;Radisky DC
培养的人肺癌细胞系已被广泛用于剖析癌症恶性肿瘤的信号通路，包括增殖和对化疗药物的耐药性。然而，恶性细胞在体内生长和转移的能力取决于特定的细胞-细胞和细胞-细胞外基质（ECM）相互作用，当细胞在传统的组织培养塑料上培养时，其中许多相互作用是不存在的。先前的研究发现，乳腺癌细胞系在富含层粘连蛋白 (lr) ECM 的三维 (3D) 凝胶中表现出不同的生长形态，并且 3D lrECM 中与组织细胞结构相关的基因表达模式与乳腺癌患者的预后相关。我们在此表明，已建立的肺癌细胞系也可以根据 lrECM 中的生长分为不同的形态类别，并且区分传统组织培养塑料上的生长和 3D lrECM 中的生长的转录改变反映了组织特异性分化。我们进一步表明，区分在 3D lrECM 中生长为平滑结构与分支结构的肺细胞系的基因表达差异可用于将腺癌患者分层为具有显着不同结果的预后组，将对 3D lrECM 的表型反应定义为肺癌恶性肿瘤的潜在替代指标。
Cultured human lung cancer cell lines have been used extensively to dissect signaling pathways underlying cancer malignancy, including proliferation and resistance to chemotherapeutic agents. However, the ability of malignant cells to grow and metastasize in vivo is dependent upon specific cell-cell and cell-extracellular matrix (ECM) interactions, many of which are absent when cells are cultured on conventional tissue culture plastic. Previous studies have found that breast cancer cell lines show differential growth morphologies in three-dimensional (3D) gels of laminin-rich (lr) ECM, and that gene expression patterns associated with organized cell structure in 3D lrECM were associated with breast cancer patient prognosis. We show here that established lung cancer cell lines also can be classified by growth in lrECM into different morphological categories and that transcriptional alterations distinguishing growth on conventional tissue culture plastic from growth in 3D lrECM are reflective of tissue-specific differentiation. We further show that gene expression differences that distinguish lung cell lines that grow as smooth vs. branched structures in 3D lrECM can be used to stratify adenocarcinoma patients into prognostic groups with significantly different outcome, defining phenotypic response to 3D lrECM as a potential surrogate of lung cancer malignancy.
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