Department of Biological Chemistry, School of Sciences, University of Buenos Aires, Ciudad Universitaria, Pabellon II, 2do Piso (1428), Buenos Aires, Argentina-CONICET.
Curr Pharm Biotechnol. 2011 Nov;12(11):1867-80. doi: 10.2174/138920111798376996.
The metastatic cascade and colonization remains a major challenge in clinical therapeutics. The formation of metastasis has many rate limiting steps. The expression of metastases initiation genes in primary tumors is driven by the need for cell motility, invasiveness, handling the shear stress in the vasculature and lymphatic circulation, and the survival and persistent growth in the distant organ. However, the expression of the progression genes in the primary tumors has a more complex basis. These metastasis-prone genes support primary tumor growth through one particular effect, whereas they enhance distant metastasis through another effect. The boundaries between metastasis initiation and metastasis progression genes are not rigid. In this review, we examine novel gene signatures identified in metastases, address key inflammatory factors mastering homing selection, gain further mechanistic insights into cell plasticity and evaluate the role of microRNAs. Moreover, we also describe the recent progress in developing nanoparticle imaging substantiating a promising theranostic platform for future cancer diagnostics and treatment, and assess the relevance of the bioinformatic analysis of metastasis-related proteins with an eye toward the metastatic niche. All these tools will provide valuable biological information of the progression of the disease, helping find potential therapeutic targets and improving surgical procedures. In a near future the understanding of the molecular mechanisms in tumor dissemination will be pivotal for the translation of these methods to the clinic and will help to overcome the barriers in clinical therapy of metastases.
转移级联和定植仍然是临床治疗的主要挑战。转移的形成有许多限速步骤。原发肿瘤中转移起始基因的表达是由细胞运动性、侵袭性、处理血管和淋巴管中的剪切力以及在远处器官中的存活和持续生长的需要所驱动的。然而，原发肿瘤中进展基因的表达具有更复杂的基础。这些易转移基因通过一种特定的效应支持原发肿瘤的生长，而通过另一种效应增强远处转移。转移起始和转移进展基因之间的界限不是固定的。在这篇综述中，我们检查了在转移中鉴定的新基因特征，讨论了掌握归巢选择的关键炎症因子，进一步深入了解细胞可塑性，并评估了 microRNAs 的作用。此外，我们还描述了开发纳米颗粒成像的最新进展，为未来癌症诊断和治疗提供了有前途的治疗平台，并评估了转移相关蛋白的生物信息学分析与转移性生态位的相关性。所有这些工具将提供疾病进展的有价值的生物学信息，有助于发现潜在的治疗靶点并改进手术程序。在不久的将来，对肿瘤播散中分子机制的理解对于将这些方法转化为临床应用至关重要，并将有助于克服临床治疗转移的障碍。
