Novel insights into the link between fetal cell microchimerism and maternal cancers.

Abstract

Fetal cell microchimerism (FCM) is defined as the persistence of fetal cells in the mother for decades after pregnancy without any apparent rejection. Fetal microchimeric cells (fmcs) engraft the maternal bone marrow and are able to migrate through the circulation and to reach tissues. In malignancies, the possible role of fmcs is still controversial, several studies advising a protective and repairing function, and other postulating a beneficial role in the progression of the disease. At the peripheral blood level, FCM is less frequently observed in women with several solid and hematological neoplasia with respect to healthy controls, suggesting a beneficial role in cancer surveillance. At the tissue level, fmcs were documented in neoplastic lesions of thyroid, breast, cervix, lung and melanoma, displaying epithelial, hematopoietic, mesenchymal and endothelial lineage differentiation. Fmcs expressing hematopoietic markers were hypothesized to have a role in the attack to neoplastic cells, whereas those expressing epithelial or mesenchymal antigens could be involved in repair and replacement of damaged cells. On the other hand, fetal cells showing an endothelial phenotype could have a role in tumor evolution and progression. The positive effect of FCM is supported by findings in animal models. This review provides an extensive overview of the link between fetal cell microchimerism and maternal cancers. Moreover, biological mechanisms by which fetal cell microchimerism is believed to modulate the protection against cancer development or tumor progression will be discussed, together with findings in animal models.