摘要
目前的医学文献说明,胚胎微环境能够抑制肿瘤的发展。在器官形成时期口服致癌物质事实上会导致胚胎畸形,但不会使后代产生肿瘤。一旦器官形成期结束,口服致癌物质会导致后代肿瘤发展起来。这些数据表明,癌症可以被认为是正常发展的分化,也受到胚胎微环境的调节。此外事实证明,一旦植入新胚胎,畸胎瘤会分化为正常组织。最近,科学家在斑马鱼胚胎中植入了一个黑色素瘤,然而却并没有导致它肿瘤的发展,相反,在成人标本中发生了。这表明在胚胎植入时,癌细胞可以分化成正常组织。此外,还表明在胚胎植入时,其他肿瘤可以恢复到一个正常的表型和/或分化成正常的组织。这些研究导致了一些作者将癌症定义为发育生物学的一个问题,并预测了目前的“癌症干细胞理论”的概念。在这篇综述中,我们记录了关于肿瘤细胞的重新编程和分化治疗的最重要的研究,以更好地阐明如何从胚胎或其他生物的物质中提取出可以诱导分化的恶性细胞。最后,文中提出的一个我们设想的模型与现实相一致,并已经被大量的研究所证明。该模型结合了B设想的“成熟逮捕”的癌症细胞的理论。贯穿整个癌症的理论描述道,作为一个由分化细胞确定的基因和/或表观改变的混乱过程,会导致正常细胞的癌变。在这里所描述的所有的研究表明,癌症可以被认为是一个发展生物学的问题,在其他文章中已经描述的分化的损失是癌症的最重要的标志之一。
关键词: 癌症;干细胞;癌干细胞;分化因子;胚胎;表观遗传调控;肿瘤细胞分化和再编程。
Current Drug Targets
Title:Cancer: A Problem of Developmental Biology; Scientific Evidence for Reprogramming and Differentiation Therapy
Volume: 17 Issue: 10
Author(s): Stewart Sell, Andrea Nicolini, Paola Ferrari, Pier M. Biava
Affiliation:
关键词: 癌症;干细胞;癌干细胞;分化因子;胚胎;表观遗传调控;肿瘤细胞分化和再编程。
摘要: Current medical literature acknowledges that embryonic micro-environment is able to suppress tumor development. Administering carcinogenic substances during organogenesis in fact leads to embryonic malformations, but not to offspring tumor growth. Once organogenesis has ended, administration of carcinogenic substances causes a rise in offspring tumor development. These data indicate that cancer can be considered a deviation in normal development, which can be regulated by factors of the embryonic microenvironment. Furthermore, it has been demonstrated that teratoma differentiates into normal tissues once it is implanted in the embryo. Recently, it has been shown that implanting a melanoma in Zebrafish embryo did not result in a tumor development; however, it did in the adult specimen. This demonstrates that cancer cells can differentiate into normal tissues when implanted in the embryo. In addition, it was demonstrated that other tumors can revert into a normal phenotype and/or differentiate into normal tissue when implanted in the embryo. These studies led some authors to define cancer as a problem of developmental biology and to predict the present concept of "cancer stem cells theory". In this review, we record the most important researches about the reprogramming and differentiation treatments of cancer cells to better clarify how the substances taken from developing embryo or other biological substances can induce differentiation of malignant cells. Lastly, a model of cancer has been proposed here, conceived by one of us, which is consistent with the reality, as demonstrated by a great number of researches. This model integrates the theory of the "maturation arrest" of cancer cells as conceived by B. Pierce with the theory which describes cancer as a process of deterministic chaos determined by genetic and/or epigenetic alterations in differentiated cells, which leads a normal cell to become cancerous. All the researches here described demonstrated that cancer can be considered a problem of developmental biology and that one of the most important hallmarks of cancer is the loss of differentiation as already described by us in other articles.
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Stewart Sell, Andrea Nicolini, Paola Ferrari, Pier M. Biava , Cancer: A Problem of Developmental Biology; Scientific Evidence for Reprogramming and Differentiation Therapy, Current Drug Targets 2016; 17 (10) . https://dx.doi.org/10.2174/1389450116666150907102717
DOI https://dx.doi.org/10.2174/1389450116666150907102717 |
Print ISSN 1389-4501 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-5592 |
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