Tumourigenesis: the subterfuge of selection

Abstract

Variation of rearrangement of regulatory genes is responsible for cellular malignant change. These types of chromosomal variations also produce heterochrony or paedomorphic evolution at the organismal level. Analogously, neoplasia represents a cellular 'macroevolutionary' event, and a tumour can be said to be an evolved population of cells. To understand this cellular evolution to malignancy, it may be necessary to go beyond a 'clonal selection' (adaptationist) explanation of neoplastic alteration. In the pericellular environment 'natural selection' consists of the organizational restraints of surrounding cells as well as the host's immunological surveillance and non-specific monocyte-macrophage systems. Indirect evidence suggests that success for the neoplasm depends not upon 'clonal selection', but solely upon a genetic methodology-the function of which is to elude selection. The author has coined the term 'cellular heterochrony' to illustrate analogic similarities in the molecular modes of speciation between anaplastic cancer cells and the heterochronic evolution of organisms. By reverting to juvenile (embryonic) repertoire of cellular behaviour a tumour secures its own tenure or niche by usurping the host's armamentarium of selection forces, employing many of the same or similar methods by which implanting and invading tissues of the mammalian embryo forestall maternal detection and rejection. A number of ways by which the tumour blocks, subverts or evades selection are discussed.

Positive selection in the evolution of cancer

“…For such cases, we hypothesize that antagonistic coevolution has led to the evolution of genetic and epigenetic (Ohlsson et al, 2003) pathways that are readily coopted or subverted by cancer cells, because they allow for rapid cell proliferation or avoidance of control by tumour suppressors or the immune system. Such subversion is seen most clearly in virus-host coevolutionary interactions, for the linkages between invasive placentation or embryonic development and cancer (Pearson, 1981(Pearson, , 1982da Costa, 2001 ;Old, 2001;Lala et al, 2002 ;Zygmunt et al, 2003), and for the associations between gametogenesis and cancer (Kleene, 2005). Signal transduction (i. e., communication within and between cells ; see also Krakauer & Pagel, 1996 ;Møller & Pagel, 1998) represents one of the main mechanisms mediating carcinogensis ; signal transduction genes have been strongly positively selected in the human and chimpanzee lineages (Clark et al, 2003), and modeling of this process using complex adaptive systems theory (Schwab & Pienta, 1997) is leading to novel insights regarding the somatic evolution of cancer.…”

“…Indeed, invasive placentation shares many biochemical and physiological features with the development of cancer (Pearson, 1981;Adamson, 1987 ;Old, 2001 ;Zygmunt et al, 2003), and stimulation of blood vessel formation may be similar between these two processes. This hypothesis could be tested further by comparing ANG evolution in eutherian mammal lineages with invasive versus non-invasive placentation (Mossman, 1987), and via analysis of the functional effects of ANG mutants during placentation and carcinogenesis.…”

“…Given its role in placental development, ANG may be subject to the parent-offspring conflicts over resource transfer that are an integral part of placentation and pregnancy (Haig, 1993(Haig, , 1999Zhang & Rosenberg, 2002 ;Crespi & Semeniuk, 2004), with cancer as a side effect of the 'tugof-war ' over the levels of placental development. Indeed, invasive placentation shares many biochemical and physiological features with the development of cancer (Pearson, 1981;Adamson, 1987 ;Old, 2001 ;Zygmunt et al, 2003), and stimulation of blood vessel formation may be similar between these two processes. This hypothesis could be tested further by comparing ANG evolution in eutherian mammal lineages with invasive versus non-invasive placentation (Mossman, 1987), and via analysis of the functional effects of ANG mutants during placentation and carcinogenesis.…”

Amphibian regeneration and cellular heterochrony

“…The term 'cellular heterochrony' has been coined (Pearson, 1981) *Uriel's term, 'retrodifferentiation' (1979) will be used throughout, instead of 'dedifferentiation' which appears most commonly in the literature on regeneration.…”

The Animal Within: Carcinogenesis and the Clonal Evolution of Cancer Cells Are Speciation Events Sensu Stricto

“…Although some authors have readily drawn an analogy between the conventional speciation of organisms, and the development of cancer (Pearson 1981;Vineis 2003) few have advanced the "cancer as species" hypothesis as a matter of fact. Two notable exceptions have been Duesberg and Rasnick (2000) and Huxley (1956).…”