Tumors are widespread among multicellular organisms. Comparative oncology generalized that neoplasia could be a property of all or most multicellular organisms but tumors are more frequent among the “higher” forms, e.g., insects and vertebrates, and in the evolutionarily more successful groups of organisms, e.g., in teleost fishes compared with cartilaginous fishes.

Ancient origin, occurrence in all multicellular organisms, and conservatism of cellular oncogenes and tumor suppressor genes support the concept that tumors are characteristic to all multicellular organisms and suggest that these genes have an important physiologic and evolutionary role. The wide occurrence of tumors and tumor-like processes in multicellular organisms, tumors’ connection to evolutionary success and progressive evolution, and the wide distribution and conservatism of cellular oncogenes suggest that tumors and/or some tumor-like processes could play the role in evolution of multicellular organisms.

Keywords

tumors; cellular oncogenes; widespread

3.1 Comparative Oncological Data on the Prevalence of Tumors in Different Groups of Multicellular Organisms

The origins of comparative oncology can be traced to 1802, when one of the scientific societies of Edinburgh raised the question of whether diseases reminiscent of human cancer occur in “brute creatures” [Dawe, 1969]. The cellular composition of human tumors was established in 1838 [Muller, 1838]. Before the end of the 19th century, tumors were discovered (with microscopic identification) in domestic animals [Leblanc, 1858], fishes [Bugnion, 1875], and mollusks [Ryder, 1887; Williams, 1890; Collinge, 1891].

In the 20th century, considerable efforts have been devoted to comparative oncological studies. Hundreds of papers on this topic were published, although some groups of multicellular organisms were studied less thoroughly than others. The first reviews of the field appeared [Willis, 1953; Huxley, 1958]. Special symposiums were organized, such as the Symposium on Neoplasms and Related Disorders of Invertebrate and Lower Vertebrate Animals held at the Smithsonian Institution, Washington, D.C. in 1968; several voluminous US National Cancer Institute monographs [Dawe and Harshbarger, 1969; Ziegler, 1980] and dozens of other monographs on comparative neoplasia were published; a special Registry of Tumors in Lower Animals was established by the U.S. National Cancer Institute to facilitate the comparative study of tumorigenesis and related disorders in invertebrate and poikilothermic vertebrate animals and to serve as a center of information and specimen reference material [Harshbarger, 1969]; a similar effort – The Veterinary Medical Data Program – was organized by the National Cancer Institute to collect data on the spontaneous occurrence of neoplasms in domestic animals [Priester, 1980]; etc.

All these efforts resulted in significant progress in the field of comparative oncology. Besides Vertebrata, tumors and tumor-like conditions have been described in Cephalochordata (lancelets), Urochordata (tunicates) and Echinodermata (echinoderms); in Protozoa, Coelenterata, Platyhelminthes, Annelida, Sipunculida, Arthropoda (predominantly in Insects) and Mollusca [Dawe and Harshbarger, 1969]. In a later publication, John Harshbarger, who for a long period of time directed the Registry of Tumors in Lower Animals, defined more exactly that “neoplasms have been found in all classes of cold-blooded animals in phylum Chordata (reptiles, amphibians, bony fish, cartilaginous fish, lampreys and hagfish) and in four of 28 phyla of invertebrates (mollusks, arthropods, platyhelminthes and cnidarians)… Additional unconfirmed neoplasm-like lesions have been reported or are being studied in several other invertebrate phyla including Sipuncula, Annelida and Echinodermata.” Therefore, concludes Harshbarger, the number of phyla with characterized neoplasms is subject to expansion [Harshbarger, 1997]. Still later, Harshbarger stated that there is conclusive evidence that cancer exists throughout the phylogenetic tree [ZoomInfo, 2013].

As important steps, the discovery of neoplasm-like lesion in urochordates as early as in 1901 [Siedlecki, 1901] and the chemical induction of lethal atypical mesenchymal proliferation in echinoderms [Tchakhotine, 1938] should be mentioned. Tumors have even been discovered in dinosaur fossils [Moodie, 1917].

It was found that in plants, a variety of environmental impacts may result in continuing proliferative responses leading to tumor-like growths. Plant tumors may be caused by different pathogens or may be genetically determined [Dodueva et al., 2007]. Moreover, some plant tumors, including the so-called crown galls, which develop under the effect of the tumor-inducing bacterium Agrobacterium tumefaciens discovered in 1907 [Smith and Townsend, 1907], show many similarities with the tumors of animals.

The discovery and studies of transmissible tumors and their causative agents in new species or classes of animals and plants had exceptional value. For example, the discovery of transmissible avian sarcoma and its filterable causative agent in 1910–1913 [Rous, 1910, 1911; Rous and Murphy, 1913] significantly influenced the whole field of fundamental oncology and paved the way for the major breakthrough in molecular oncology in subsequent years. This discovery was honored by Nobel Prize awarded to Peyton Rous in 1967.

A lot of discussions were devoted to the difficulties in discrimination between neoplasia, hyperplasia, and response to injury or parasitic invasion in invertebrates and lower vertebrates. Many researchers questioned the occurrence of “true” neoplasms in these animals.

“…The paucity of information about neoplasms of mollusks and other invertebrates makes the distinction between neoplasia, hyperplasia, and response to injury or infection difficult to determine confidently, mainly because there are no trenchant established criteria to diagnose neoplasia in these animals… In some cases gross lesions observed were thought to be neoplastic until histologic examination revealed them to be inflammatory responses or parasitic infestations. Growths do exist that are difficult to classify as either reactive or neoplastic” [Pauley, 1969].

“…In the invertebrates, … many structures described as tumors in the literature are clearly hyperplasias or unusual proliferations of typical cellular components in response to injury or parasitic invasion and would not be considered tumors by the concepts developed in pathology of vertebrates. Points of difference that permit distinction between neoplastic and non-neoplastic changes are perhaps debatable and require experimental study not usually possible with the small numbers of tumors recognized among invertebrates in nature” [Sparks, 1969].

“It is recognized that a biological definition of neoplasia is not generally applicable … because the biological potential of most tumors in these animals remains unknown. It is therefore necessary to base diagnostic judgments largely on the classical morphological criteria of the pathologist. Historically derived from studies of mammalian tissues, these criteria include increased mitotic rate, anaplasia, invasion, and metastasis. Their general validity among lower vertebrates and invertebrates is not yet firmly established” [Wellings, 1969].

Not only histological methodology of neoplastic versus non-neoplastic differentiation may cause the problem, but the line between hyperplasia and neoplasia could be as uncertain biochemically and physiologically as it is histologically [Grizzle and Goodwin, 1998]. This and similar opinions would suggest the possibility of the existence of some borderline tumor-like processes, a possibility that will be important for my future considerations of what processes could supply evolving multicellular organisms with extra cell masses for the origin of new cell types, tissues and organs.

Understanding of neoplasms achieved through studies of mammalian tumors and tumors of other higher vertebrates may not be applicable to tumors of lower vertebrates and invertebrates because of the biological differences1.

“…The differences between neoplasms of invertebrates and of vertebrates may be so great that we fail to recognize their nature and kinship” [Dawe, 1969].

“…The criteria used in mammalian classification schemes may not be adequate for lower vertebrates due to the biologic differences among vertebrates, and because these criteria have generally been developed in a clinical context to provide prognostic information that generally does not apply to lower vertebrates including fishes”[Groff, 2004].

For example, information concerning the clinical consequence or outcome of the majority of neoplasms in fishes is, on the whole, non-existent. The adverse effects of fish tumors are not always obvious and it seems that in wild fish neoplasms do not affect the size of fish populations. Neoplasms in fishes are generally less aggressive and more differentiated than neoplasms in mammals. They are mostly discrete, focal, benign neoplasms. The most important feature of few malignant fish neoplasms is local invasion: they rarely exhibit metastatic behavior. That is why invasiveness is the...