Hematopoietic progenitor cells as possible origins of epithelial thymoma in a human T lymphocyte virus type I pX gene transgenic rat model

Tsuchikawa, Takahiro; Ikeda, Hitoshi; Kikuchi, Kazunori; Tsuji, Takahiro; Baba, Tomohisa; Ishizu, Akihiro; Tanaka, Yuetsu; Kato, Hiroyuki; Yoshiki, Takashi

doi:10.1038/labinvest.3700028

Cited by 6 publications

(3 citation statements)

References 35 publications

(31 reference statements)

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“…5 In addition, in a human T-lymphocyte virus transgenic rat model, hematopoietic progenitor cells give rise to epithelial thymomas. 6 A skin carcinoma in a human female receiving a kidney graft from a male donor contained Yþ cells in tumor nests, 7 and various other cancers in human females receiving male donor BM transplants have been found to contain about 1:10,000 cancer cells with the Y chromosome, suggesting a process called developmental mimicry. 8 We originally sought to test the hypothesis that BMDSCs could give rise to liver cancer.…”

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confidence: 99%

Direct and indirect contribution of bone marrow‐derived cells to cancer

Guest

Ilić²,

Ma³

et al. 2010

Intl Journal of Cancer

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Stromal-epithelial interactions may control the growth and initiation of cancers. Here, we not only test the hypothesis that bone marrow-derived cells may effect development of cancers arising from other tissue cells by forming tumor stroma but also that sarcomas may arise by transformation of stem cells from the bone marrow and epithelial cancers may arise by transdifferentiation of bone marrow stem cells to epithelial cancers. Lethally irradiated female FVB/N mice were restored with bone marrow (BM) transplants from a male transgenic mouse carrying the polyoma middle T-oncoprotein under the control of the mouse mammary tumor virus promoter (MMTV-PyMT) and followed for development of lesions. All of 8 lethally irradiated female FVB/N recipient mice, restored with BM transplants from a male MMTV-PyMT transgenic mouse, developed Y-chromosome negative (Y2) cancers of various organs surrounded by Y1 stroma. One of the female FVB/N recipient mice also developed fibrosarcoma and 1, a diploid breast adenocarcinoma containing Y chromosomes. In contrast, only 1 of 12 control female mice restored with normal male BM developed a tumor (lymphoma) during the same time period. These results indicate not only that the transgenic BM-derived stromal cells may indirectly contribute to development of tumors in recipient mice but also that sarcomas may arise by transformation of BM stem cells and that breast cancers arise by transdifferentiation of BM stem cells, presumably by mesenchymal-epithelial transition.

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confidence: 99%

Direct and indirect contribution of bone marrow‐derived cells to cancer

Guest

Ilić²,

Ma³

et al. 2010

Intl Journal of Cancer

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“…The authors detected high levels of pX mRNA in thymomas compared with controls, suggesting a possible role of HTLV‐I pX in the development of thymomas 41 . These findings were further implicated by the results in another study where epithelial thymoma developed in the thymus of transgenic rats expressing pX, thereby providing possible evidence for HTLV‐involvement in thymomas 46 …”

Section: Viral Infection In the Pathogenesis Of Thymoma And Related Diseasesmentioning

confidence: 82%

“… 41 These findings were further implicated by the results in another study where epithelial thymoma developed in the thymus of transgenic rats expressing pX, thereby providing possible evidence for HTLV‐involvement in thymomas. 46 …”

Section: Viral Infection In the Pathogenesis Of Thymoma And Related Diseasesmentioning

confidence: 99%

Viral infection in thymoma and thymic tumors with autoimmune diseases

Chang

Duan

et al. 2021

Thoracic Cancer

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A thymoma is a type of thymic tumor which is rarely malignant that is frequently reported in adult patients. A number of thymoma‐related immune disorders are observed including autoimmune diseases, which suggests a strong connection between thymoma development and immunological mechanisms. Characterized by association with humoral and cellular immunodeficiency, thymoma patients are susceptible to opportunistic infections by environmental factors. Recent reports have suggested that viral infection may play a role in the etiological mechanisms of thymoma development associated with dysregulated immunity. In this review, we summarize the case reports and studies related to viral infection, such as CMV, EBV and HSV, that probably play a part in the pathogenesis of thymoma and related diseases. Furthermore, we demonstrate the underlying mechanisms by which viruses may induce the occurrence of thymoma with autoimmune diseases. Lastly, we discuss the potential application of antiviral therapy in the treatment of thymic diseases.

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Chronic graft-versus-host disease-like autoimmune disorders spontaneously occurred in rats with neonatal thymus atrophy

et al. 2005

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We earlier reported that the human T cell leukemia virus type-1 pX gene transduced into rat thymic epithelial cells had an impact on biology of the cells. We report here that FWpX rats born by mating of F344 transgenic rats expressing the pX gene without tissue specificity with nontransgenic Wistar rats developed disorders, including atrophy of the thymus, lymphocytopenia, and inflammatory cell infiltration into multiple organs, similar to events in chronic graft-vs.-host disease (GVHD). Vanishment of thymic epithelial cells especially in the cortex and marked depletion of CD4 CD8 doublepositive thymocytes were evident in the neonatal thymus in these rats. The relative abundance of CD8 compared to CD4 T cells may be related to dominant infiltration of CD8 T cells into the affected organs. Additionally, adoptive transfer of FW-pX splenocytes could induce lymphocytic infiltration into sublethally irradiated wild-type syngeneic recipients. Analysis of the expression level of the Foxp3 gene in peripheral blood mononuclear cells revealed that the numbers of immunoregulatory T cells were less in FW-pX rats than in wild-type rats. The collective evidence suggested that the FWpX rats spontaneously developed chronic GVHD-like autoimmune diseases, following abortive differentiation of T cells in the thymus in early days of the newborn. This rat model may shed light on the pathogenesis of chronic GVHD and also other systemic autoimmune diseases, the etiology of which is unknown.

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Hematopoietic progenitor cells as possible origins of epithelial thymoma in a human T lymphocyte virus type I pX gene transgenic rat model

Cited by 6 publications

References 35 publications

Direct and indirect contribution of bone marrow‐derived cells to cancer

Direct and indirect contribution of bone marrow‐derived cells to cancer

Viral infection in thymoma and thymic tumors with autoimmune diseases

Chronic graft-versus-host disease-like autoimmune disorders spontaneously occurred in rats with neonatal thymus atrophy

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