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Contents : Vol 443 7 September 2006 NEWS & VIEWS CANCER BIOLOGY Infectious tumour cells David Dingli and Martin A. Nowak The current view of cancer development is that normal cells are transformed into tumour cells by sequential mutations that activate cancerpromoting oncogenes or inhibit genes that would otherwise suppress tumours or trigger genetic instabilities. As a consequence every tumour is the result of a unique evolutionary process as the cancer cells adapt to out-compete their neighbours. This process begins in its individual host and ends with the elimination of the tumour or the death of the host. Two studies1 2 however suggest that some tumour cells can behave like infectious agents and move from one host to another. It has long been suspected that canine transmissible venereal tumour (CTVT) is transferred between dogs by implantation of tumour cells from the donor to the recipient where the tumour grows as a graft (Fig. 1)3. Several lines of evidence provided indirect support for this hypothesis. A tumour can only be induced by the implantation of whole CTVT cells and not by cell extracts or dead cells. Normal canine cells have 78 chromosomes but the tumour cells isolated from different animals characteristically have 58 to 59 chromosomes4. In addition a particular insertion near the c-myc oncogene is present in all tumour samples5. If the graft transfer hypothesis is correct tumour cells from different animals should all be similar genetically and should be different from the normal cells of the host animal. Writing in Cell Murgia et al.1 now provide a formal proof of the graft hypothesis for CTVT. They studied CTVT cells and normal cells isolated from dogs from five continents. They show that all the tumours are closely related genetically and different from normal cells of the host dog by using a combination of genetic techniques (dog leukocyte antigen (DLA) haplotyping microsatellite DNA and mitochondrial DNA sequencing). The tumours from different animals had less genetic variability than that observed within even the most inbred breed of dog. Therefore the tumours could not have arisen from the separate cancerous transformations of cells within individual animals but have been transmitted from one dog to another spreading from an ancestral clone. Murgia et al.1 estimate that C. MURGIA Cancer cells are generally viewed as a problem innate to their host but evidence is mounting that they can evolve to become infectious agents and be transmitted between individuals. Figure 1 A canine transmissible venereal tumour in the progressive stage. this clone arose between 250 and 2 500 years ago making it the oldest known continuously replicating cancer cell line in animals1. In an independent study Pearse and Swift2 reported that devil facial tumour disease is caused by tumour cell transmission between Tasmanian devils. Cancer cells isolated from different animals with tumours of different age and size have the same pattern of chromosomal abnormalities. Furthermore all the normal cells from one animal had part of one chromosome inverted but this inversion was not found in any of the tumour cells from that animal suggesting that the tumour did not arise from host cells. So can infectious transmission of cancer also occur between people There is no evidence (yet) for direct person-to-person transmission of tumour cells during normal social contact. The only known physiological route for tumour cell transmission in humans is during pregnancy. In the United States every year about 3 500 pregnant women also have a malignancy and transplacental transmission of acute leukaemia lymphoma melanoma and carcinoma from mother to fetus has been observed6. Acute leukaemia cells have also been transferred between fetuses in mothers with a multiple pregnancy followed by the development of disease in both fetuses6. Organ transplantation is another possible route of tumour cell transmission between people. The immunosuppressive therapy required for survival of the transplanted organ blunts the immune surveillance that might otherwise recognize and react against donor-derived tumour cells. Fortunately the development of donor-derived tumours is rare: 0.04% of solid organ transplant recipients develop a cancer that was transferred from their donor7 and 0.06% of recipients of haematopoetic stemcell transplants develop blood cancers from the transferred cells8. The main culprit seems to be malignant melanoma that is undetected in the donor at the time of organ harvest7. Finally we came across a case report where a surgeon developed malignant fibrous histiocytoma after accidentally injuring his palm during surgical removal of the tumour from a patient9. Why is cancer in general not transmissible between people A main reason is tissue graft rejection caused by so-called MHC incompatibility. In humans and other vertebrates the immune system uses cell-surface proteins called MHC antig

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