文章：

弥散性肿瘤细胞的检测、临床相关性和特异性生物学特性

Detection, clinical relevance and specific biological properties of disseminating tumour cells

原文发布日期：2008-05-01

DOI: 10.1038/nrc2375

类型: Review Article

开放获取: 否

要点：

1. Tumour cell dissemination is an early event in tumorigenesis and is relevant for metastatic progression (in particular for breast cancer). These data have led to the introduction of disseminating tumour cells (DTCs) in international tumour classification systems.
2. Bone marrow (BM) is a common homing organ for tumour cells that are derived from various types of epithelial tumours including breast, prostate and colon cancer. Tumour cells may either establish overt metastases in the BM, as is seen for patients with breast or prostate cancer, or re-circulate to other organs, such as liver or lung, where they find better growth conditions, as is evident in patients with colon cancer.
3. Significant technical advancements in immunological procedures and quantitative real-time PCR-based assays now allow DTCs to be identified and enumerated at frequencies of 1 per 10⁶–10⁷ nucleated blood or BM cells.
4. Sophisticated molecular techniques such as whole-genome analysis or gene expression profiling have been applied to obtain initial information on the molecular characteristics of DTCs. The current data indicate that most DTCs are dormant (non-proliferative) in situ. However, these cells are viable and can proliferate in cell culture in response to appropriate growth factors, such as the stem cell growth factors epidermal growth factor (EGF) and fibroblast growth factor 2 (FGF2).
5. DTCs can express cancer stem cell profiles (such as CD44⁺/CD24⁻ in breast cancer patients) and exhibit stem cell properties such as resistance to chemotherapy and long-term persistence in the BM.
6. Identification of therapeutic targets on DTCs and circulating tumour cells (CTCs) and real-time monitoring of CTCs in cancer patients undergoing systemic therapy are the most important future clinical applications. In this context, the ERBB2 proto-oncogene has served as a proof-of-principle target for the monitoring and treatment of DTCs in human breast cancer.

要点翻译：

1. 肿瘤细胞播散是肿瘤发生过程中的早期事件，并与转移进展相关（尤其在乳腺癌中）。这些数据促使国际肿瘤分类系统引入了播散性肿瘤细胞（DTCs）的概念。
2. 骨髓是各类上皮源性肿瘤细胞（包括乳腺癌、前列腺癌和结肠癌）常见的归巢器官。肿瘤细胞既可在骨髓中形成明显转移灶（如乳腺癌或前列腺癌患者），也可重新循环至肝、肺等其他生长条件更适宜的器官（如结肠癌患者所示）。
3. 免疫学检测技术和定量实时PCR方法的重大进展，目前可在每10^6–10^7个有核血液或骨髓细胞中识别并计数DTCs。
4. 全基因组分析或基因表达谱分析等精密分子技术已被应用于获取DTCs分子特征的初步信息。现有数据表明大多数DTCs在病灶处处于休眠状态（非增殖性）。但这些细胞具有活性，在适当生长因子（如表皮生长因子和成纤维细胞生长因子2等干细胞生长因子）刺激下可在细胞培养中增殖。
5. DTCs可表达癌症干细胞特征（如乳腺癌患者的CD44+/CD24−表型），并呈现干细胞特性，包括化疗耐药性和在骨髓中的长期持续存在。
6. 针对DTCs和循环肿瘤细胞寻找治疗靶点，以及对接受全身治疗的癌症患者进行实时CTC监测，是未来最重要的临床应用方向。其中ERBB2原癌基因已作为乳腺癌患者DTCs监测与治疗的原理验证靶点。

英文摘要：

Most cancer deaths are caused by haematogenous metastatic spread and subsequent growth of tumour cells at distant organs. Disseminating tumour cells present in the peripheral blood and bone marrow can now be detected and characterized at the single-cell level. These cells are highly relevant to the study of the biology of early metastatic spread and provide a diagnostic source in patients with overt metastases. Here we review the evidence that disseminating tumour cells have a variety of uses for understanding tumour biology and improving cancer treatment.

摘要翻译： 

大多数癌症死亡是由血源性转移扩散及肿瘤细胞在远处器官的生长所致。现在，外周血和骨髓中的播散性肿瘤细胞可在单细胞水平被检测和表征。这些细胞与早期转移扩散生物学研究高度相关，并为已有明显转移的患者提供诊断来源。在此，我们综述了播散性肿瘤细胞在理解肿瘤生物学和改善癌症治疗方面具有多种用途的证据。

原文链接：

Detection, clinical relevance and specific biological properties of disseminating tumour cells