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转移:固有表型与获得性表型。

Metastasis: inherent vs. acquired phenotype.

机构信息

Department of Clinical Laboratory, Tangdu Hospital, Shaanxi, PR China.

出版信息

Med Hypotheses. 2010 May;74(5):874-6. doi: 10.1016/j.mehy.2009.11.023. Epub 2009 Dec 16.

Abstract

The problem how tumor cells get the metastatic ability is still a hot debate. Based on the premise that the default state of normal cells is quiescent rather than mobile, the classic progression and early metastasis model suggested that tumor metastasis should be an acquired trait contributed by the late or early gene mutations during carcinogenesis. Here, an inherent metastasis model is proposed that the metastatic ability of the tumor cells is one of the constitutive features of the normal cells of tumor origin. The idea is based on two facts. One is that tumor arises from stem or progenitor cells and in turn are driven by tumor stem cells. The other is that emerging evidence showing that a small population of stem or progenitor cells has the inherent migration capacity in normal development and adulthood. This inherent metastatic model has some implications. First, metastatic dissemination should occur continually throughout the course of primary tumor development and generate a diverse spectrum of disseminated cells. Second, most of the disseminated tumor cells should have the stem cell like features. Third, migration of stem cells and cancer cells should invoke similar molecular processes involving metastasis. Fourth, genomic alterations that primarily promote the production of tumor cells with stem cell traits, i.e., tumor stem cell, exacerbate tumor progression and metastasis. Finally, overt metastatic production is primarily determined by whether the disseminated tumor cells can survive and grow into overt metastatic foci at the ectopic sites, instead of that whether the tumor cells can leave the primary sites and travel to other sites. All these predictions have gotten increasing supporting evidences. Yet, to confirm whether the new paradigm is true or false, it needs carefully examine whether normal stem or progenitor cells of various tissues have the potential to traveling and arriving at the ectopic sites. Furthermore, exploiting the mechanisms for regulating normal stem or progenitor cells migration may provide more critical results for our deeply understanding the secrets of tumor metastasis and offer new methods for preventing and treating tumor metastasis.

摘要

肿瘤细胞如何获得转移能力仍然是一个热门的争论话题。基于正常细胞的默认状态是静止而不是运动的前提,经典的进展和早期转移模型表明,肿瘤转移应该是癌变过程中晚期或早期基因突变赋予的获得性特征。在这里,提出了一个固有转移模型,即肿瘤细胞的转移能力是肿瘤起源的正常细胞的固有特征之一。这个想法基于两个事实。一个是肿瘤起源于干细胞或祖细胞,反过来又受肿瘤干细胞的驱动。另一个是越来越多的证据表明,一小部分干细胞或祖细胞在正常发育和成年期具有内在的迁移能力。这个固有转移模型有一些含义。首先,转移扩散应该在原发性肿瘤发展的整个过程中持续发生,并产生多样化的扩散细胞。其次,大多数扩散的肿瘤细胞应该具有干细胞样特征。第三,干细胞和癌细胞的迁移应该涉及类似的分子过程,包括转移。第四,主要促进产生具有干细胞特征的肿瘤细胞的基因组改变,即肿瘤干细胞,会加剧肿瘤的进展和转移。最后,明显的转移产生主要取决于扩散的肿瘤细胞是否能够在异位部位存活并生长为明显的转移灶,而不是肿瘤细胞是否能够离开原发部位并转移到其他部位。所有这些预测都得到了越来越多的支持证据。然而,为了确定新的范式是正确还是错误,需要仔细检查各种组织的正常干细胞或祖细胞是否具有迁移到异位部位的潜力。此外,利用调节正常干细胞或祖细胞迁移的机制可能为我们深入了解肿瘤转移的秘密提供更关键的结果,并为预防和治疗肿瘤转移提供新的方法。

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