Cancer in the parasitic protozoans Trypanosoma brucei and Toxoplasma gondii

Abstract

Cancer is a general name for more than 100 malignant diseases. It is postulated that all cancers start from a single abnormal cell that grows out of control. Untreated cancers can cause serious consequences and deaths. Great progress has been made in cancer research that has significantly improved our knowledge and understanding of the nature and mechanisms of the disease, but the origins of cancer are far from being well understood due to the limitations of suitable model systems and to the complexities of the disease. In view of the fact that cancers are found in various species of vertebrates and other metazoa, here, we suggest that cancer also occurs in parasitic protozoans such as Trypanosoma brucei, a blood parasite, and Toxoplasma gondii, an obligate intracellular pathogen. Without treatment, these protozoan cancers may cause severe disease and death in mammals, including humans. The simpler genomes of these single-cell organisms, in combination with their complex life cycles and fascinating life cycle differentiation processes, may help us to better understand the origins of cancers and, in particular, leukemias.

Keywords: evolution; malignancy; mammals; single-cell organisms; transmissible.

Fig. 1.

Differences between normal and cancer cells. Normal cells arise from stem cells that differentiate to specific cell types that carry out specific functions. Cancer cells lose the division limitation owing to various reasons (e.g., nDNA or mtDNA mutations or damage) and lose the ability to differentiate into specific cell types, as well as being unable to carry out specific physiological functions. During the evolution of a cancer, several mutations in genomes can occur and accumulate. Each factor increases the possibility of occurrence of mutations, insertions, deletions, or epigenetic effects that are linked to a cancer. Adapted from the National Cancer Institute (www.cancer.gov).

Fig. 2.

Life cycles of T. brucei and T. evansi. (I) Life cycle of T. brucei (with fully functioning kDNA). Blood slender (normal) forms (stage A) differentiate, via an intermediate stage (stage B), into the stumpy form (stage C), which is the only stage with the necessary specific functions for infecting the insect vector. Once in the insect host (stages D–F), only the metacyclic form (stage F) in the vector can infect the mammalian host and differentiate into the slender form. The infected host can survive longer due to the regulated parasite growth and differentiation. (II) Life cycle of T. evansi (considered a mutant strain of T. brucei). Only the blood slender form (stage A) is found. It replicates directly (stages A and B), but it cannot differentiate into the stumpy form (similar to the dedifferentiation in a cancer cell). It loses the ability to infect the insect vector (cannot survive and differentiate within the insect vector). Some natural hosts can be killed by the infection of this parasite in a short time, depending on the mammalian species.

Fig. 3.

(I) Life cycle of WT T. gondii. Tachyzoites (stage A) can differentiate into bradyzoites (stage B) in definitive or intermediate hosts and can differentiate into oocysts (stage E) in the definitive host (feline animals, cats) after sexual reproduction (stages C and D). Both parasite and host can survive in most cases depending on the life span of the host. (II) RH strain, a mutant strain of WT T. gondii. The tachyzoite (stage A) cannot differentiate into the bradyzoite in either the intermediate or the definitive host and cannot differentiate into oocysts in the definitive host. It reproduces by reinfection of host cells (stage B). The hosts will normally be killed by the parasites or vice versa.

Fig. 4.

Transmission routes of protozoan parasites and infectious or noninfectious cancers in nature and the laboratory. Naturally, T. evansi, the cancer of T. brucei we considered, and the devil facial tumor disease (DFTD) can be mechanically transmitted by the biting of insects or the devil itself. T. equiperdum, the other cancer of T. brucei and canine transmissible venereal tumor (CTVT) can be naturally transmitted by intercourse between hosts. All strains of T. evansi, T. equiperdum, T. gondii RH, and most cancers can be mechanically transmitted from individual to individual by syringe in laboratory.