Circulation DNA: Biological implications for cancer metastasis and immunology
Circulation DNA: Biological implications for cancer metastasis and immunology
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DOI：
10.1016/j.mehy.2005.04.042
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发表时间：
2005-01-01
影响因子：
4.7
通讯作者：
Xia, Y
中科院分区：
文献类型：
--
作者：
Chen, Z;Fadiel, A;Xia, Y
循环细胞游离DNA（cf-DNA）对于寻求分离特定癌症标志物的肿瘤学研究人员来说是相当感兴趣的。在这里，我们专注于cf-DNA的起源和生物学意义，探索其在癌症生物学和医学中的潜在作用。我们假设除了凋亡或坏死的癌细胞之外，cf-DNA主要由活癌细胞释放，原因有三：（1）在放射治疗后，尽管预期辐射诱导的大量凋亡，但cf-DNA量在高百分比的患者中显著降低;（2）当存在很少凋亡或坏死细胞时，培养上清液中的癌细胞DNA浓度随着细胞增殖而增加;（3）正常淋巴细胞培养物经植物血凝素、脂多糖或抗原刺激后DNA浓度增加。我们的假设在癌症生物学中具有重要的生物学意义。首先，癌症cf-DNA可以转化正常细胞并形成邻近或远端转移灶或第二原发癌。在这方面，我们还提出了一个令人震惊的建议，即癌症可能具有潜在的传染性。其次，如果正常的cf-DNA含有细胞因子序列，它可能表现得像一种内在的DNA疫苗，产生治疗性细胞因子。如果正常cf-DNA含有非突变的癌基因或肿瘤抑制基因的序列，则可能发生与癌症基因组的同源重组，导致敲除突变的癌基因或肿瘤抑制基因，从而引起癌症的自发缓解。(c)2005爱思唯尔有限公司保留所有权利。
Circulation cell free DNA (cf-DNA) is of considerable interest to oncology researchers seeking to isolate specific cancer markers. Here, we focus on the origin and biological implications of cf-DNA, exploring its potential roles in cancer biology and medicine. We hypothesize that cf-DNA is primarily released by living cancer cells in addition to apoptotic or necrotic cancer cells for three reasons: (1) following radiotherapy, cf-DNA quantities are significantly reduced in a high percentage of patients although radiation -induced massive apoptosis is expected; (2) cancer cell DNA concentration in cultured supernatants increases with cell proliferation when few apoptotic or necrotic cells are present; and (3) DNA concentration increases in normal lymphocyte cultures following stimulation with phytohemagglutinin, lipopolysaccharide or antigen. Our hypotheses have major biological implications in cancer biology. First, cancer cf-DNA may transform normal cells and form adjacent or remote metastases or second primary cancer. In this context, we also have raised an alarming advice that the cancer may be potentially infectious. Secondly, if a normal cf-DNA contains cytokine sequence, it may behave Like an intrinsic DNA vaccine, producing therapeutic cytokine. If normal cf-DNA contains a sequence of a non-mutated oncogene or tumor suppressor gene, homologous recombination with the cancer genome may occur leading to knock out mutated oncogene or tumor suppressor gene that could thus elicit a spontaneous remission of cancer. (c) 2005 Elsevier Ltd. All rights reserved.