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.
