Death-from-cancer signatures and stem cell contribution to metastatic cancer
Death-from-cancer signatures and stem cell contribution to metastatic cancer
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DOI：
10.4161/cc.4.9.2001
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发表时间：
2005-09-01
期刊：
影响因子：
4.3
通讯作者：
Glinsky, GV
中科院分区：
文献类型：
--
作者：
Glinsky, GV
全基因组表达谱研究揭示了一种转录上不同的人类实体瘤亚型，在诊断为各种起源的早期癌症的癌症患者中具有明显的转移性播散倾向、高度恶性的临床行为和较差的治疗结果。这一肿瘤亚组在肿瘤进展早期获得完全转移潜力，包括出现和接种有效的转移前体细胞。总的来说，这些数据表明，这种转录定义的亚型的人癌的高度恶性的突变等位基因组合的早期参与发展，赋予转移的倾向和/或参与干细胞和/或早期祖细胞的转化和肿瘤进展。用正常干细胞富集原发性肿瘤增加了干细胞和癌细胞之间通过细胞融合和/或摄取凋亡小体进行水平基因组转移（DNA和染色质的大规模转移）的可能性，并产生具有自我更新的高度恶性表型的重编程体细胞杂交体。
Genome-wide expression profiling studies reveal a transcriptionally distinct sub-type of human solid tumors with a marked propensity toward metastatic dissemination, highly malignant clinical behavior, and poor therapy outcome in cancer patients diagnosed with the early stage carcinomas of various origins. This sub-set of tumors acquires full metastatic potential, including an emergence and seeding of potent metastasis precursor cells, early in tumor progression. Collectively, these data suggest an early involvement in development of this transcriptionally defined sub-type of human carcinomas of a highly malignant combination of mutant alleles conferring the proclivity to metastasize and/or an engagement in transformation and tumor progression of stem cells and/or early progenitor cells. Enrichment of primary tumors with normal stem cells increases the likelihood of horizontal genomic transfer ( large-scale transfer of DNA and chromatin) between stem cells and cancer cells via cell fusion and/or uptake of apoptotic bodies and generation of reprogrammed somatic cell hybrids with self-renewing highly malignant phenotype.