Transcriptomic signature of cell lines isolated from canine mammary adenocarcinoma metastases to lungs
Transcriptomic signature of cell lines isolated from canine mammary adenocarcinoma metastases to lungs
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DOI：
10.1007/bf03195709
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发表时间：
2010-01-01
影响因子：
2.4
通讯作者：
Motyl, T.
中科院分区：
文献类型：
--
作者：
Krol, M.;Polanska, J.;Motyl, T.
转移是乳腺癌进展的最后一步，通常导致死亡。潜在地，转移的分子特征可以通过比较原发转移者与其转移来定义。目前，文献中没有关于犬转移瘤分子特征的数据，关于人类癌症的报告也很少。这是第一份描述犬癌转移细胞转录组特征的报告。从犬乳腺中分离的两种腺癌细胞系（CMT-W1和CMT-W2）与从其肺转移瘤中分离的细胞系（CMT-W1M和CMT-W2M）进行了比较，涉及以下细胞计数参数：细胞周期、倍性、Bcl-2表达、诱导凋亡的敏感性和转录组学特征。流式细胞仪分析显示，在细胞周期和抗凋亡潜力的显着差异之间的检查细胞。使用寡核苷酸芯片，我们发现104个上调基因在转移细胞系CMT-W1M和21个上调基因在原代CMT-W1细胞系。在CMT-W2细胞系中，我们还发现了83个上调基因，而在CMT-W2细胞系中只有21个上调基因。在两种转移细胞系中上调的基因中，我们发现了15个共同的基因。这些不同表达的基因主要涉及信号转导、细胞结构和运动性、核酸代谢、发育过程和凋亡（GHSR、RASSF1、ARF1GAP、WDR74、SMOC2、SFRP 4、DIAPHI、FSCNI、ALX 4、SNX 15、PLD 2、WNT 7B、POU 6F2、NKG 7和POLR 2F）。其中7个参与生长激素促分泌素受体（GHSR）依赖于ghrelin的细胞途径。我们的研究结果表明，这一途径可能是乳腺癌细胞具有转移潜力所必需的。
Metastasis is a final step in the progression of mammary gland cancer, usually leading to death. Potentially, a molecular signature of metastasis can be defined via comparison of primary turners with their metastases. Currently, there is no data in the literature regarding the molecular portrait of metastases in dogs and only few reports regarding human cancer. This is the first report describing the transcriptomic signature of canine cancer metastatic cells. Two adenocarcinoma cell lines isolated from the canine mammary gland (CMT-W1 and CMT-W2) were compared with cell lines isolated from their lung metastases (CMT-W1M and CMT-W2M) with regards to the following cytometric parameters: cell cycle, ploidy, Bcl-2 expression, susceptibility to induced apoptosis, and transcriptomic profile. Cytometric analyses revealed significant differences in cell cycle and antiapoptotic potential between the examined cells. Using oligonucleotide microarrays, we found 104 up-regulated genes in the metastatic cell line CMT-W1M and 21 up-regulated genes in the primary CMT-W1 cell line. We also found 83 up-regulated genes in the CMT-W2M cell line and only 21 Up-regulated genes in the CMT-W2 cell line. Among the up-regulated genes in both metastatic cell lines, we found 15 common genes. These differently expressed genes are involved mainly in signal transduction, cell structure and motility, nucleic acid metabolism, developmental processing, and apoptosis (GHSR, RASSF1, ARF1GAP, WDR74, SMOC2, SFRP4, DIAPHI, FSCNI, ALX4, SNX15, PLD2, WNT7B, POU6F2, NKG7, and POLR2F). Seven of them are involved in a cellular pathway dependent on ghrelin via growth hormone secretagogue receptor (GHSR). Our results suggest that this pathway may be essential for mammary cancer cells to have a metastatic potential.