Advertisement

Chimerism pp 181-194 | Cite as

Cancer

  • Valentina Cirello
  • Laura Fugazzola
Chapter

Abstract

The 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.

Keywords

Microchimerism Fetal microchimeric cells Pregnancy Cancer Pregnancy-associated progenitor cells 

References

  1. 1.
    Stevens AM, Hermes HM, Lambert NC, Nelson JL, Meroni PL, Cimaz R. Maternal and sibling microchimerism in twins and triplets discordant for neonatal lupus syndrome-congenital heart block. Rheumatology (Oxford). 2005;44:187–91.CrossRefGoogle Scholar
  2. 2.
    Sato T, Fujimori K, Sato A, Ohto H. Microchimerism after induced or spontaneous abortion. Obstet Gynecol. 2008;112:593–7.CrossRefPubMedGoogle Scholar
  3. 3.
    Khosrotehrani K, Johnson KL, Lau J, Dupuy A, Cha DH, Bianchi DW. The influence of fetal loss on the presence of fetal cell microchimerism: a systematic review. Arthritis Rheum. 2003;48:3237–41.CrossRefPubMedGoogle Scholar
  4. 4.
    Peterson SE, Nelson JL, Gadi VK, Gammill HS. Fetal cellular microchimerism in miscarriage and pregnancy termination. Chimerism. 2013;4:136–8.CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Gammill HS, Stephenson MD, Aydelotte TM, Nelson JL. Microchimerism in recurrent miscarriage. Cell Mol Immunol. 2014;11:589–94.CrossRefPubMedPubMedCentralGoogle Scholar
  6. 6.
    Seppanen E, Fisk NM, Khosrotehrani K. Pregnancy-acquired fetal progenitor cells. J Reprod Immunol. 2013;97:27–35.CrossRefPubMedGoogle Scholar
  7. 7.
    Gammill HS, Guthrie KA, Aydelotte TM, Adams Waldorf KM, Nelson JL. Effect of parity on fetal and maternal microchimerism: interaction of grafts within a host? Blood. 2010;116:2706–12.CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Mold JE, Michaëlsson J, Burt TD, Muench MO, Beckerman KP, Busch MP, Lee TH, Nixon DF, McCune JM. Maternal alloantigens promote the development of tolerogenic fetal regulatory T cells in utero. Science. 2008;322:1562–5.CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Gammill HS, Adams Waldorf KM, Aydelotte TM, Lucas J, Leisenring WM, Lambert NC, Nelson JL. Pregnancy, microchimerism, and the maternal grandmother. PLoS One. 2011;6:e24101.CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Cirello V, Perrino M, Colombo C, Muzza M, Filopanti M, Vicentini L, Beck-Peccoz P, Fugazzola L. Fetal cell microchimerism in papillary thyroid cancer: studies in peripheral blood and tissues. Int J Cancer. 2010;126:2874–8.PubMedGoogle Scholar
  11. 11.
    Lambert NC, Erickson TD, Yan Z, Pang JM, Guthrie KA, Furst DE, Nelson JL. Quantification of maternal microchimerism by HLA-specific real-time polymerase chain reaction: studies of healthy women and women with scleroderma. Arthritis Rheum. 2004;50:906–14.CrossRefPubMedGoogle Scholar
  12. 12.
    Khosrotehrani K, Stroh H, Bianchi DW, Johnson KL. Combined FISH and immunolabeling on paraffin-embedded tissue sections for the study of microchimerism. Biotechniques. 2003;34(2):242–4.PubMedGoogle Scholar
  13. 13.
    Ariga H, Ohto H, Busch MP, Imamura S, Watson R, Reed W, Lee TH. Kinetics of fetal cellular and cell-free DNA in the maternal circulation during and after pregnancy: implications for noninvasive prenatal diagnosis. Transfusion. 2001;41:1524–30.CrossRefPubMedGoogle Scholar
  14. 14.
    Bianchi DW, Zickwolf GK, Weil GJ, Sylvester S, DeMaria MA. Male fetal progenitor cells persist in maternal blood for as long as 27 years postpartum. Proc Natl Acad Sci U S A. 1996;93:705–8.CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    O’Donoghue K, Chan J, de la Fuente J, Kennea N, Sandison A, Anderson JR, Roberts IA, Fisk NM. Microchimerism in female bone marrow and bone decades after fetal mesenchymal stem-cell trafficking in pregnancy. Lancet. 2004;364:179–82.CrossRefPubMedGoogle Scholar
  16. 16.
    Lambert NC, Lo YM, Erickson TD, Tylee TS, Guthrie KA, Furst DE, Nelson JL. Male microchimerism in healthy women and women with scleroderma: cells or circulating DNA? A quantitative answer. Blood. 2002;100:2845–51.CrossRefPubMedGoogle Scholar
  17. 17.
    Evans PC, Lambert N, Maloney S, Furst DE, Moore JM, Nelson JL. Long-term fetal microchimerism in peripheral blood mononuclear cell subsets in healthy women and women with scleroderma. Blood. 1999;93:2033–7.PubMedPubMedCentralGoogle Scholar
  18. 18.
    Khosrotehrani K, Bianchi DW. Multi-lineage potential of fetal cells in maternal tissue: a legacy in reverse. J Cell Sci. 2005;118:1559–63.CrossRefPubMedGoogle Scholar
  19. 19.
    Parant O, Dubernard G, Challier JC, Oster M, Uzan S, Aractingi S, Khosrotehrani K. CD34+ cells in maternal placental blood are mainly fetal in origin and express endothelial markers. Lab Investig. 2009;89:915–23.CrossRefPubMedGoogle Scholar
  20. 20.
    Kara RJ, Bolli P, Karakikes I, Matsunaga I, Tripodi J, Tanweer O, Altman P, Shachter NS, Nakano A, Najfeld V, Chaudhry HW. Fetal cells traffic to injured maternal myocardium and undergo cardiac differentiation. Circ Res. 2012;110:82–93.CrossRefPubMedGoogle Scholar
  21. 21.
    Rijnink EC, Penning ME, Wolterbeek R, Wilhelmus S, Zandbergen M, van Duinen SG, Schutte J, Bruijn JA, Bajema IM. Tissue microchimerism is increased during pregnancy: a human autopsy study. Mol Hum Reprod. 2015;21:857–64.CrossRefPubMedGoogle Scholar
  22. 22.
    Fujiki Y, Johnson KL, Tighiouart H, Peter I, Bianchi DW. Fetomaternal trafficking in the mouse increases as delivery approaches and is highest in the maternal lung. Biol Reprod. 2008;79:841–8.CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Johnson KL, Bianchi DW. Fetal cells in maternal tissue following pregnancy: what are the consequences? Hum Reprod Update. 2004;10:497–502.CrossRefPubMedGoogle Scholar
  24. 24.
    Sunami R, Komuro M, Yuminamochi T, Hoshi K, Hirata S. Fetal cell microchimerism develops through the migration of fetus-derived cells to the maternal organs early after implantation. J Reprod Immunol. 2010;84:117–23.CrossRefPubMedGoogle Scholar
  25. 25.
    Khosrotehrani K, Reyes RR, Johnson KL, Freeman RB, Salomon RN, Peter I, Stroh H, Guégan S, Bianchi DW. Fetal cells participate over time in the response to specific types of murine maternal hepatic injury. Hum Reprod. 2007;22:654–61.CrossRefPubMedGoogle Scholar
  26. 26.
    Khosrotehrani K, Leduc M, Bachy V, Nguyen Huu S, Oster M, Abbas A, Uzan S, Aractingi S. Pregnancy allows the transfer and differentiation of fetal lymphoid progenitors into functional T and B cells in mothers. J Immunol. 2008;180(2):889–97.CrossRefPubMedGoogle Scholar
  27. 27.
    Nguyen Huu S, Oster M, Uzan S, Chareyre F, Aractingi S, Khosrotehrani K. Maternal neoangiogenesis during pregnancy partly derives from fetal endothelial progenitor cells. Proc Natl Acad Sci U S A. 2007;104:1871–6.CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Nguyen Huu S, Khosrotehrani K, Oster M, Moguelet P, Espié MJ, Aractingi S. Early phase of maternal skin carcinogenesis recruits long-term engrafted fetal cells. Int J Cancer. 2008;123:2512.CrossRefPubMedGoogle Scholar
  29. 29.
    Nguyen Huu S, Oster M, Avril MF, Boitier F, Mortier L, Richard MA, Kerob D, Maubec E, Souteyrand P, Moguelet P, Khosrotehrani K, Aractingi S. Fetal microchimeric cells participate in tumour angiogenesis in melanomas occurring during pregnancy. Am J Pathol. 2009;174:630–7.CrossRefPubMedPubMedCentralGoogle Scholar
  30. 30.
    Tan XW, Liao H, Sun L, Okabe M, Xiao ZC, Dawe GS. Fetal microchimerism in the maternal mouse brain: a novel population of fetal progenitor or stem cells able to cross the blood-brain barrier? Stem Cells. 2005;23:1443–52.CrossRefPubMedGoogle Scholar
  31. 31.
    Zeng XX, Tan KH, Yeo A, Sasajala P, Tan X, Xiao ZC, Dawe G, Udolph G. Pregnancy-associated progenitor cells differentiate and mature into neurons in the maternal brain. Stem Cells Dev. 2010;19:1819–30.CrossRefPubMedGoogle Scholar
  32. 32.
    Wang Y, Iwatani H, Ito T, Horimoto N, Yamato M, Matsui I, Imai E, Hori M. Fetal cells in mother rats contribute to the remodeling of liver and kidney after injury. Biochem Biophys Res Commun. 2004;325:961–7.CrossRefPubMedGoogle Scholar
  33. 33.
    Dubernard G, Aractingi S, Oster M, Rouzier R, Mathieu MC, Uzan S, Khosrotehrani K. Breast cancer stroma frequently recruits fetal derived cells during pregnancy. Breast Cancer Res. 2008;10:R14.CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Dubernard G, Oster M, Chareyre F, Antoine M, Rouzier R, Uzan S, Aractingi S, Khosrotehrani K. Increased fetal cell microchimerism in high grade breast carcinomas occurring during pregnancy. Int J Cancer. 2009;124:1054–9.CrossRefPubMedGoogle Scholar
  35. 35.
    Castela M, Nassar D, Sbeih M, Jachiet M, Wang Z, Aractingi S. Ccl2/Ccr2 signalling recruits a distinct fetal microchimeric population that rescues delayed maternal wound healing. Nat Commun. 2017;8:15463.CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Tokita K, Terasaki P, Maruya E, Saji H. Tumor regression following stem cell infusion from daughter to microchimeric mother. Lancet. 2001;358:2047–8.CrossRefPubMedGoogle Scholar
  37. 37.
    Cha D, Khosrotehrani K, Kim Y, Stroh H, Bianchi DW, Johnson KL. Cervical cancer and microchimerism. Obstet Gynecol. 2003;102:774–81.PubMedGoogle Scholar
  38. 38.
    Gadi VK, Nelson JL. Fetal microchimerism in women with breast cancer. Cancer Res. 2007;67:9035–8.CrossRefPubMedGoogle Scholar
  39. 39.
    Gadi VK, Malone KE, Guthrie KA, Porter PL, Nelson JL. Case-control study of fetal microchimerism and breast cancer. PLoS One. 2008;3:e1706.CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Gadi VK. Fetal microchiemrism in breast from women with and without breast cancer. Breast Cancer Res Treat. 2010;121:241–4.CrossRefPubMedGoogle Scholar
  41. 41.
    Cirello V, Recalcati MP, Muzza M, Rossi S, Perrino M, Vicentini L, Beck-Peccoz P, Finelli P, Fugazzola L. Fetal cell microchimerism in papillary thyroid cancer: a possible role in tumor damage and tissue repair. Cancer Res. 2008;68:8482–8.CrossRefPubMedGoogle Scholar
  42. 42.
    Cirello V, Colombo C, Perrino M, De Leo S, Muzza M, Maffini MA, Fugazzola L. Fetal cell microchimerism in papillary thyroid cancer: a role in the outcome of the disease. Int J Cancer. 2015;137:2989–93.CrossRefPubMedGoogle Scholar
  43. 43.
    Gilmore GL, Haq B, Shadduck RK, Jasthy SL, Lister J. Fetal-maternal microchimerism in normal parous females and parous female cancer patients. Exp Hematol. 2008;36:1073–7.CrossRefPubMedGoogle Scholar
  44. 44.
    O’Donoghue K, Sultan HA, Al-Allaf FA, Anderson JR, Wyatt-Ashmead J, Fisk NM. Microchimeric fetal cells cluster at sites of tissue injury in lung decades after pregnancy. Reprod Biomed Online. 2008;16:382–90.CrossRefPubMedGoogle Scholar
  45. 45.
    Khosrotehrani K, Nguyen Huu S, Prignon A, Avril MF, Boitier F, Oster M, Mortier L, Richard MA, Maubec E, Kerob D, Mansard S, Merheb C, Moguelet P, Nassar D, Guegan S, Aractingi S. Pregnancy promotes melanoma metastasis through enhanced lymphangiogenesis. Am J Pathol. 2011;178:1870–80.CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Kamper-Jørgensen M, Biggar RJ, Tjønneland A, Hjalgrim H, Kroman N, Rostgaard K, Stamper CL, Olsen A, Andersen AM, Gadi VK. Opposite effects of microchimerism on breast and colon cancer. Eur J Cancer. 2012;48:2227–35.CrossRefPubMedGoogle Scholar
  47. 47.
    Dhimolea E, Denes V, Lakk M, Al-Bazzaz S, Aziz-Zaman S, Pilichowska M, Geck P. High male chimerism in the female breast shows quantitative links with cancer. Int J Cancer. 2013;133:835–42.CrossRefPubMedGoogle Scholar
  48. 48.
    Eun JK, Guthrie KA, Zirpoli G, Gadi VK. In situ breast cancer and microchimerism. Sci Rep. 2013;3:2192.CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Hromadnikova I, Kotlabova K, Pirkova P, Libalova P, Vernerova Z, Svoboda B, Kucera E. The occurrence of fetal microchimeric cells in endometrial tissues is a very common phenomenon in benign uterine disorders, and the lower prevalence of fetal microchimerism is associated with better uterine cancer prognoses. DNA Cell Biol. 2014;33:40–8.CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Nemescu D, Ursu RG, Nemescu ER, Negura L. Heterogeneous distribution of fetal microchimerism in local breast cancer environment. PLoS One. 2016;11:e0147675.CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Jolis TW, Brucker BM, Schorl C, Butera JN, Quesenberry PJ. Low microchimeric cell density in tumors suggests alternative antineoplastic mechanism. Med Oncol. 2017;34:65.CrossRefPubMedGoogle Scholar
  52. 52.
    Broestl L, Rubin JB, Dahiya S. Fetal microchimerism in human brain tumors. Brain Pathol. 2017.  https://doi.org/10.1111/bpa.12557. [Epub ahead of print].
  53. 53.
    Thliveris AT, Schwefel B, Clipson L, Plesh L, Zahm CD, Leystra AA, Washington MK, Sullivan R, Deming DA, Newton MA, Halberg RB. Transformation of epithelial cells through recruitment leads to polyclonal intestinal tumors. Proc Natl Acad Sci U S A. 2013;110:11523–8.CrossRefGoogle Scholar
  54. 54.
    Kamper-Jørgensen M. Microchimerism and survival after breast and colon cancer diagnosis. Chimerism. 2012;3:72–3.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer International Publishing AG, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Division of Endocrine and Metabolic DiseasesIstituto Auxologico Italiano - IRCCSMilanItaly
  2. 2.Department of Pathophysiology and TransplantationUniversity of MilanMilanItaly

Personalised recommendations