Skin Carcinoma Arising From Donor Cells in a Kidney Transplant Recipient

Aractingi, S.; Kanitakis, Jean; Euvrard, Sylvie; Danff, Caroline Le; Péguillet, Isabelle; Khosrotehrani, Kiarash; Lantz, Olivier; Carosella, Edgardo D.

doi:10.1158/0008-5472.can-04-2783

Cited by 91 publications

(63 citation statements)

References 30 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…There is now a substantial body of evidence that BMDCs contribute to cancer in both human (12)(13)(14)(15) and mouse models (3,(16)(17)(18)(19) as tumor cells and as stromal cells. In the mouse model of chronic Helicobacter felis-induced gastric cancer, gastric cancer originates from a marrow-derived cell (3) and requires that the BM stem cell spends an extended period replicating within the peripheral tissue (3).…”

Section: Introductionmentioning

confidence: 99%

Spontaneous Expression of Embryonic Factors and p53 Point Mutations in Aged Mesenchymal Stem Cells: A Model of Age-Related Tumorigenesis In Mice

et al. 2007

View full text Add to dashboard Cite

Aging is the single most common risk factor for cancer. Peripheral and marrow-derived stem cells are long lived and are candidate cells for the cancer-initiating cell. Repeated rounds of replication are likely required for accumulation of the necessary genetic mutations. Based on the facts that mesenchymal stem cells (MSC) transform with higher frequency than other cell types, and tumors in aged C57BL/6 mice are frequently fibrosarcomas, we used a genetically tagged bone marrow (BM) transplant model to show that aged mice develop MSC-derived fibrosarcomas. We further show that, with aging, MSCs spontaneously transform in culture and, when placed into our mouse model, recapitulated the naturally occurring fibrosarcomas of the aged mice with gene expression changes and p53 mutation similar to the in vivo model. Spontaneously transformed MSCs contribute directly to the tumor, tumor vasculature, and tumor adipose tissue, recruit additional host BM-derived cells (BMDC) to the area, and fuse with the host BMDC. Unfused transformed MSCs act as the cancer stem cell and are able to form tumors in successive mice, whereas fusion restores a nonmalignant phenotype. These data suggest that MSCs may play a key role in age-related tumors, and fusion with host cells restores a nonmalignant phenotype, thereby providing a mechanism for regulating tumor cell activity. [Cancer Res 2007;67(22):10889-98]

show abstract

Section: Introductionmentioning

confidence: 99%

Spontaneous Expression of Embryonic Factors and p53 Point Mutations in Aged Mesenchymal Stem Cells: A Model of Age-Related Tumorigenesis In Mice

et al. 2007

View full text Add to dashboard Cite

show abstract

“…More surprising was the identification of a donor-derived genotype in epithelial cells in 4 cases of oral SCC after bone marrow transplantation (13), because this implied that donor-derived bone marrow cells, either hematopoietic or mesenchymal, yielded epithelial tumors. Donor-derived cells were also found in a skin basal cell carcinoma in a kidney transplant recipient (9), but the donor cell contribution to the malignant epithelium was not established.…”

Section: Resultsmentioning

confidence: 96%

“…Accumulation of tumor-suppressing p53 is significantly associated with these squamous cell carcinomas (SCCs) (7), and TP53 mutations are found in tumor cells (8). In a series of kidney transplant recipients, tumor cells of donor genotype have been identified in 1 skin basal cell carcinoma (9), but the type of donor cell that homed to the skin remains to be characterized. In addition, there was no evidence of a donor epithelial cell contributing to the malignant epithelium in the recipient.…”

Section: Introductionmentioning

confidence: 99%

Human skin carcinoma arising from kidney transplant–derived tumor cells

Verneuil¹,

Varna²,

Ratajczak³

et al. 2013

J. Clin. Invest.

View full text Add to dashboard Cite

Tumor cells with donor genotype have been identified in human skin cancer after allogeneic transplantation; however, the donor contribution to the malignant epithelium has not been established. Kidney transplant recipients have an increased risk of invasive skin squamous cell carcinoma (SCC), which is associated with accumulation of the tumor suppressor p53 and TP53 mutations. In 21 skin SCCs from kidney transplant recipients, we systematically assessed p53 expression and donor/recipient origin in laser-microdissected p53 + tumor cells. In one patient, molecular analyses demonstrated that skin tumor cells had the donor genotype and harbored a TP53 mutation in codon 175. In a kidney graft biopsy performed 7 years before the skin SCC diagnosis, we found p53 + cells in the renal tubules. We identified the same TP53 mutation in these p53 + epithelial cells from the kidney transplant. These findings provide evidence for a donor epithelial cell contribution to the malignant skin epithelium in the recipient in the setting of allogeneic kidney transplantation. This finding has theoretical implications for cancer initiation and progression and clinical implications in the context of prolonged immunosuppression and longer survival of kidney transplant patients.

show abstract

“…Indeed, we were able to find that chimeric cells originating from a grafted kidney appeared to frequently invade skin cancers or their precursors, actinic keratosis. 15 Therefore, tumour developmentincluding skin carcinogenesis-appears to frequently lead to the accumulation of microchimeric cells, even if these result from previous pregnancies. However, in the present case, none of the tumours was entirely composed of fetal cells.…”

Section: Discussionmentioning

confidence: 99%

“…14 We have recently described the participation of donor derived cells in malignant skin tumours developing after organ transplantation. 15 In one case, the tumour was composed of donor derived keratinocytes suggesting that progenitor cells of donor origin had engrafted in the recipient skin and underwent transformation upon exposure to carcinogenic stimuli. However, in most cases of this study, skin tumours contained chimeric cells but did not originate from these.…”

mentioning

confidence: 99%

Early phase of maternal skin carcinogenesis recruits long‐term engrafted fetal cells

Huu

Khosrotehrani

Oster

et al. 2008

Intl Journal of Cancer

Self Cite

View full text Add to dashboard Cite

During pregnancy, fetal cells enter the maternal circulation. These may be mesenchymal stem cells, haematopoietic or endothelial progenitors, which may persist for decades and be recruited to damaged maternal tissues. Recently, fetal cells were also identified in tumour tissues such as cervical cancer and breast carcinomas. However, the timing of malignant tumour infiltration was not demonstrated. In this study, we used two step carcinogenesis to assess the presence of fetal cells in early phases of skin tumour formation in previously pregnant mice. Wild-type female C57/BL6 mice were bred to transgenic mice for EGFP. After delivery, skin papillomas were induced by two-step carcinogenesis. The tumours were dissected 9 months after gestation. Fetal cells were identified in 75% of cutaneous papillomas (9/12 tumours), but never in normal skin from the same mice. Fetal cells expressed von-Willebrand factor, and less frequently CD45 or cytokeratin but did not express the tumoral epidermal keratins. Our study shows that long-term engrafted fetal cells home to early stage skin tumours where they participate in formation of the stroma. ' 2008 Wiley-Liss, Inc.Key words: two step carcinogenesis; pregnancy; fetal cells; microchimerism In a relatively frequent number of situations, a low number of donor cells are found in the peripheral blood or the tissues of a genetically different recipient. This phenomenon, called microchimerism, results mainly from pregnancy. Indeed, during gestation, fetal cells cross the placenta, enter the maternal circulation and persist after delivery in 20-50% of women.1 Solid organ transplantation, red blood cell transfusion or exchange between twins also lead to a similar microchimerism. The fetal cells transferred to the mothers include hematopoietic progenitors in humans 3,4 and mouse models 5 as well as mesenchymal stem cells.6 Several studies have shown that fetal cells are able to migrate to damaged maternal tissues such as thyroid, liver, intestine or cervix in humans 7,8 and liver, kidney, skin or brain in mouse models. [9][10][11][12] In these tissues, fetal cells may adopt the phenotype of the affected organ. 13 The participation of microchimeric cells in tumours developing in the recipient has been a subject of interest in the past years. Indeed, Kaposi sarcomas developing after kidney transplantation have been shown to derive mainly from donor cells.14 We have recently described the participation of donor derived cells in malignant skin tumours developing after organ transplantation. 15 In one case, the tumour was composed of donor derived keratinocytes suggesting that progenitor cells of donor origin had engrafted in the recipient skin and underwent transformation upon exposure to carcinogenic stimuli. However, in most cases of this study, skin tumours contained chimeric cells but did not originate from these. Besides, the participation of fetal cells in maternal tumour stroma has also been suggested in breast cancer during gestation. 16 However, to date, only few studies have consi...

show abstract

Skin Carcinoma Arising From Donor Cells in a Kidney Transplant Recipient

Cited by 91 publications

References 30 publications

Spontaneous Expression of Embryonic Factors and p53 Point Mutations in Aged Mesenchymal Stem Cells: A Model of Age-Related Tumorigenesis In Mice

Spontaneous Expression of Embryonic Factors and p53 Point Mutations in Aged Mesenchymal Stem Cells: A Model of Age-Related Tumorigenesis In Mice

Human skin carcinoma arising from kidney transplant–derived tumor cells

Early phase of maternal skin carcinogenesis recruits long‐term engrafted fetal cells

Contact Info

Product

Resources

About