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Novel insights into the link between fetal cell microchimerism and maternal cancers
No full textINTRODUCTION: 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.
CONCLUSIONS: 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
Positive effect of fetal cell microchimerism on tumor presentation and outcome in papillary thyroid cancer
No full textStudies on both circulating and tissue fetal cell microchimerism (FCM) favored its protective role in thyroid cancer, consistent with findings in other malignancies. Nevertheless, scanty data were available on the possible impact on the outcome of the disease. We demonstrated that FCM has a positive effect on thyroid cancer presentation and outcome. We also excluded that the better clinical features observed were due to the effect of pregnancy per se. In conclusion, FCM may have not only a protective role toward the onset of thyroid cancer, but also a positive effect on its progression. These findings give novel insights into the identification of the role of FCM in oncology and, consequently, in the potential therapeutic application of this physiological phenomenon
Fetal cell microchimerism in human cancers
No full textThe transfer of fetal cells into the maternal circulation occurs normally during pregnancy and the post-partum persistence of these cells in the maternal blood and tissues, known as fetal cell microchimerism, has been clearly demonstrated. However, the long-term consequences of this phenomenon are only beginning to be appreciated. In particular, whether microchimerism could be involved in the carcinogenetic process or whether fetal microchimeric cells could be able to differentiate in host tissues, participating in the maternal response to injury, is still matter of study. In this review, the possible role and the consequences of fetal cell microchimerism, as emerged from studies in animal models and in women with different types of cancer, will be presented
Fetal microchimerism as an explanation of disease
No full textFetal cell microchimerism is defined as the persistence of fetal cells in the mother after birth without any apparent rejection. Fetal microchimeric cells (FMCs) engraft into the maternal bone marrow for decades after delivery and are able to migrate to blood and tissues. This phenomenon was hypothesized to have a detrimental role in autoimmune diseases, but data are still controversial and debated. In malignant tumors, fetal cell microchimerism has been postulated to have a positive effect on tumor burden, although some evidence suggests that FMCs may be involved in neoplastic progression. At the peripheral level, circulating FMCs are less frequently detected in patients with thyroid cancer, breast cancer or other solid, hematologic malignancies than in healthy individuals, which suggests a protective role for fetal cell microchimerism. In tissues, FMCs have been found in tumor sections from malignancies such as thyroid, breast, cervix, lung cancers and melanomas and have been shown to differentiate into epithelial, hematopoietic, endothelial and mesenchymal cells. FMCs with hematopoietic differentiation have been postulated to have a role in destroying the tumor, whereas mesenchymal and epithelial cells could participate in repair processes. Endothelial cells, on the other hand, are believed to play a part in tumor progression. This Review provides an overview of the role of fetal cell microchimerism in autoimmune and benign or malignant nonautoimmune diseases. Moreover, the mechanisms by which fetal cell microchimerism is believed to modulate the protection against cancer or tumor progression will be discussed, together with future research directions
Microchimerism and endocrine disorders
No full textContext: The term "microchimerism" indicates the coexistence, in the same organism, of genetically distinct populations of cells derived from two different individuals. The passage of cells from the fetus to the mother is called fetal cell microchimerism, whereas that occurring from the mother to the fetus is named maternal cell microchimerism. Microchimeric cells can persist in blood and tissues for decades. Evidence Acquisition: A literature search through the U. S. National Library of Medicine was used to identify and review studies on maternal and fetal microchimerism, focusing on endocrine diseases. Evidence Synthesis: According to the majority of reports, fetal cell microchimerism seems to have a detrimental role in autoimmune diseases and a positive effect on tumor burden in most human cancers studied. In autoimmune thyroid diseases, fetal microchimeric cells (fmcs) have been found to be significantly more represented within the thyroid gland of women with Hashimoto's thyroiditis and Graves' disease compared to those without thyroid autoimmunity, suggesting a pathogenic role. In thyroid cancer tissues, fmcs have been found to be present at higher levels than in contralateral normal tissues and have been shown to differentiate into epithelial and hematopoietic cells. Microchimeric cells with hematopoietic differentiation could have a role in destroying the tumor, whereas epithelial cells are believed to participate in the repairing processes. At the peripheral level, circulating fmcs were less frequently detected in patients with thyroid cancer than in healthy individuals, consistent with data obtained for breast cancer and other solid and hematological malignancies, indicating a protective role against cancer development. Finally, type 1 diabetes has been mostly related to maternal cell microchimerism. Indeed, the levels of circulating maternal cells were higher in type 1 diabetes patients than in controls. At the pancreas level, female beta-cells were identified and hypothesized to be targets of autoimmunity or to regenerate diseased tissues. (J Clin Endocrinol Metab 97: 1452-1461, 2012
Cancer
No full textThe term fetal cell microchimerism (FCM) indicates the persistence of fetal cells in the mother for decades after pregnancy. These cells engraft the maternal bone marrow and are able to migrate through the circulation and to reach tissues in case of damage. In animal models, a beneficial effect of microchimeric cells in the repair of tissues after injury is documented. In humans, the possible role of fetal microchimeric cells is still controversial, particularly in the cancer field. At the peripheral blood level, FCM is less frequently observed in parous women affected with cancer than in healthy controls, suggesting a beneficial role in cancer surveillance. At the tissue level, several studies propose a protective and repair function for FCM, whereas others hypothesize a role in the progression of the disease. Interestingly, fetal microchimeric cells are able to transdifferentiate along different lineages. In particular, fetal cells expressing epithelial markers are hypothesized to have a repair function, those positive for hematopoietic markers to have a role in the attack of tumor cells, whereas those displaying an endothelial phenotype to favor tumor progression
Fetal cell microchimerism in papillary thyroid cancer : a role in the outcome of the disease
No full textFetal cell microchimerism (FCM) is defined as the persistence of fetal cells in maternal organs and circulation without any apparent rejection and it was hypothesized to protect toward the onset of some neoplastic diseases. To verify the role of FCM in papillary thyroid cancer (PTC), we enrolled 87 parous women with PTC and at least one male pregnancy preceding the diagnosis (PTC-P), 66 healthy women with 1 or more male children (HC-P) and 57 nonparous women with PTC (PTC-NP). The presence of circulating male DNA was assessed by the amplification of the Y chromosome-specific gene SRY, with a sensitivity of 1 male cell/1 million female cells. A significantly higher frequency of FCM was found in HC-P than PTC-P women (63.6% vs. 39.1%, p = 0.004). Among PTC-P patients, those positive for the presence of FCM (FMC+ve) had a lower prevalence of extrathyroidal extension (p = 0.027) and lymph node metastases (p = 0.044) than those without FCM (FMC-ve). Moreover, FMC+ve patients were more frequently in remission than FMC-ve cases (94.1 vs. 67.9%, p = 0.009). Interestingly, we showed for the first time that the positive effect on tumor presentation and outcome is specifically related to FCM and it is not an effect of pregnancy. In conclusion, circulating FCM is significantly more frequent in healthy parous women than in women with PTC. Moreover, the presence of circulating fetal male cells is associated with a significantly lower extrathyroidal extension and a good prognosis, suggesting a protective role of this phenomenon toward both the onset and the progression of thyroid cancer
Allelic distribution of six RET polymorphisms in sporadic medullary thyroid cancer and functional analysis of G691S variant
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