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

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.