AUTHOR=Manzo Giovanni 

TITLE=Defined Mathematical Relationships Among Cancer Cells Suggest Modular Growth in Tumor Progression and Highlight Developmental Features Consistent With a Para-Embryonic Nature of Cancer

JOURNAL=Frontiers in Cell and Developmental Biology

VOLUME=8

YEAR=2020

URL=https://www.frontiersin.org/journals/cell-and-developmental-biology/articles/10.3389/fcell.2020.00804

DOI=10.3389/fcell.2020.00804

ISSN=2296-634X

ABSTRACT=<p>Several similarities between the embryo development and the cancer process suggest the para-embryonic nature of tumors. Starting from an initial cancer stem cell (i-CSC) as a para-embryonic stem cell (p-ESC), a hierarchic sequence of CSCs (CSC<sub>1</sub>s, CSC<sub>2</sub>s, CSC<sub>3</sub>s) and non-CSCs [cancer progenitor cells (CPCs), cancer differentiated cells (CDCs)] would be generated, mimicking an ectopic rudimentary ontogenesis. Such a proposed heterogeneous cell hierarchy within the tumor structure would suggest a tumor growth model consistent with experimental data reported for mammary tumors. By tabulating the theoretical data according to this model, it is possible to identify defined mathematical relationships between cancer cells (CSCs and non-CSCs) that are surprisingly similar to experimental data. Moreover, starting from this model, it is possible to speculate that, during progression, tumor growth would occur in a modular way that recalls the propagation of tumor spheres <italic>in vitro</italic>. All these considerations favor a comparison among normal blastocysts (as <italic>in vitro</italic> embryos), initial avascular tumors (as <italic>in vivo</italic> abnormal blastocysts) and tumor spheres (as <italic>in vitro</italic> abnormal blastocysts). In conclusion, this work provides further support for the para-embryonic nature of the cancer process, as recently theorized.</p>