RNA Sequencing Analysis Reveals Interactions between Breast Cancer or Melanoma Cells and the Tissue Microenvironment during Brain Metastasis.
RNA Sequencing Analysis Reveals Interactions between Breast Cancer or Melanoma Cells and the Tissue Microenvironment during Brain Metastasis.
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DOI：
10.1155/2017/8032910
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发表时间：
2017
影响因子：
--
通讯作者：
Arima Y
中科院分区：
文献类型：
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作者：
Sato R;Nakano T;Hosonaga M;Sampetrean O;Harigai R;Sasaki T;Koya I;Okano H;Kudoh J;Saya H;Arima Y
转移是癌症患者治疗失败和死亡的主要原因。乳腺癌、非小细胞肺癌或黑色素瘤患者经常发生肿瘤细胞向脑部转移。尽管最近我们对原发性肿瘤的病因和治疗的理解取得了进展，但癌细胞转移到大脑的生物学和分子机制仍不清楚。转移的癌细胞与它们在大脑中的微环境相互作用以建立转移。我们现在已经建立了基于心脏内注射人类乳腺癌或黑色素瘤细胞系的小鼠脑转移模型，我们已经进行了RNA测序分析，以确定小鼠脑组织和人类癌细胞中表达与转移特异性相关的基因。我们发现小鼠基因Tph2、Sspo、Ptprq和Pole以及人类基因CXCR4、PLLP、TNFSF4、VCAM1、SLC8A2和SLC7A11在转移脑组织中表达上调。进一步表征这些有助于脑转移建立的基因可能为开发新的治疗策略和随后改善癌症患者的预后提供基础。
Metastasis is the main cause of treatment failure and death in cancer patients. Metastasis of tumor cells to the brain occurs frequently in individuals with breast cancer, non–small cell lung cancer, or melanoma. Despite recent advances in our understanding of the causes and in the treatment of primary tumors, the biological and molecular mechanisms underlying the metastasis of cancer cells to the brain have remained unclear. Metastasizing cancer cells interact with their microenvironment in the brain to establish metastases. We have now developed mouse models of brain metastasis based on intracardiac injection of human breast cancer or melanoma cell lines, and we have performed RNA sequencing analysis to identify genes in mouse brain tissue and the human cancer cells whose expression is associated specifically with metastasis. We found that the expressions of the mouse genes Tph2, Sspo, Ptprq, and Pole as well as those of the human genes CXCR4, PLLP, TNFSF4, VCAM1, SLC8A2, and SLC7A11 were upregulated in brain tissue harboring metastases. Further characterization of such genes that contribute to the establishment of brain metastases may provide a basis for the development of new therapeutic strategies and consequent improvement in the prognosis of cancer patients.