Article in Seminars in Cancer Biology · April 2008 doi: 10. 1016/j semcancer

The default state of cells in metazoa

Among microbiologists, it is axiomatic to accept that proliferation is the default state of

prokaryotes and unicellular eukaryotes [13]. It is therefore puzzling to note that the majority

of researchers delving on metazoan biology have ignored whether or not the default state of

cells in metazoa was a relevant premise to consider in this context. The nature of the default

state is not only an important theoretical issue; it has also heuristic implications. When planning

experiments, researchers implicitly or explicitly decide which premises to choose. The

adoption of one of these two alternative views determines the type of experimental program

that will be conducted, and hence, it is at the core of the research program of the competing

theories of carcinogenesis [14-16].

Based on an evolutionary perspective and on our experience using a variety of cell culture

models and their animal counterparts, we favor the concept that the default state of cells in

metazoa, like those of unicellular organisms and metaphyta, is proliferation. In a recent

revisiting of the subject, we became aware that at the end of the 19th century, the famed

pathologist H. Ribbert postulated that cancer cells, freed from the restraint of tissue structure,

would express their constitutive property to proliferate [6]. Ribbert's view was foreshadowed

by Weigert (1882) and Roux (1888)[7]. Thus, even though there is a long dating precedent for

the view that proliferation is the default state of cells, for near a century this principle has been

practically ignored both in textbooks and by experimentalists when discussing either the control

of cell proliferation or carcinogenesis. As a result, the premise that proliferation is the default

Sonnenschein and Soto

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Semin Cancer Biol. Author manuscript; available in PMC 2009 October 1.

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state of all cells failed to be incorporated among the basic tenets of experimental biology [17,

18].

We and a few others have addressed the subject while using estrogen target cells [19-21]; still

others showed that the quiescence of lymphocytes is actively maintained (i.e., it is induced)

[22,23], and that this proliferative quiescence was not just a consequence of the expression of

a cellular differentiation program, as recently suggested [18,24].