Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences (SGGW), ul. Nowoursynowska 159, 02-776 Warsaw, Poland.
J Appl Genet. 2010;51(1):37-50. doi: 10.1007/BF03195709.
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 tumors 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, DIAPH1, FSCN1, 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.
转移是乳腺癌症进展的最后一步，通常导致死亡。通过比较原发性肿瘤与其转移灶，可以确定转移的分子特征。目前，文献中没有关于狗转移灶的分子特征的数据，只有少数关于人类癌症的报道。这是第一份描述犬转移性癌细胞转录组特征的报告。我们比较了从犬乳腺（CMT-W1 和 CMT-W2）分离的两个腺癌细胞系与从其肺转移灶（CMT-W1M 和 CMT-W2M）分离的细胞系，比较了以下细胞计量学参数：细胞周期、倍性、Bcl-2 表达、对诱导凋亡的敏感性以及转录组谱。细胞计量学分析显示，检查细胞的细胞周期和抗凋亡能力存在显著差异。使用寡核苷酸微阵列，我们在转移性细胞系 CMT-W1M 中发现了 104 个上调基因，在原发性 CMT-W1 细胞系中发现了 21 个上调基因。我们还在 CMT-W2M 细胞系中发现了 83 个上调基因，而在 CMT-W2 细胞系中只发现了 21 个上调基因。在两个转移性细胞系中上调的基因中，我们发现了 15 个共同的基因。这些差异表达的基因主要参与信号转导、细胞结构和运动、核酸代谢、发育加工和细胞凋亡（GHSR、RASSF1、ARF1GAP、WDR74、SMOC2、SFRP4、DIAPH1、FSCN1、ALX4、SNX15、PLD2、WNT7B、POU6F2、NKG7 和 POLR2F）。其中 7 个基因参与了一个依赖于生长激素释放肽受体（GHSR）的 ghrelin 细胞通路。我们的结果表明，该通路可能对乳腺癌细胞具有转移潜能至关重要。
