Early phase of maternal skin carcinogenesis recruits long-term engrafted fetal cells
Sau Nguyen Huu
Developmental Physiopathology Laboratory, UPMC Univ Paris 06, EA4053, Paris, France
Team 15, INSERM UMRS-893, CDR Saint-Antoine, Paris, France
Search for more papers by this authorCorresponding Author
Kiarash Khosrotehrani
Developmental Physiopathology Laboratory, UPMC Univ Paris 06, EA4053, Paris, France
Team 15, INSERM UMRS-893, CDR Saint-Antoine, Paris, France
Department of Dermatology, AP-HP, Hôpital Tenon, Paris, France
Fax: +33156016458.
Department of Dermatology, AP-HP, Hôpital Tenon, 4 rue de la Chine, 75020 Paris, FranceSearch for more papers by this authorMichèle Oster
Developmental Physiopathology Laboratory, UPMC Univ Paris 06, EA4053, Paris, France
Team 15, INSERM UMRS-893, CDR Saint-Antoine, Paris, France
Search for more papers by this authorPhilippe Moguelet
Department of Pathology, AP-HP, Hôpital Tenon, Paris, France
Search for more papers by this authorMarie-Josée Espié
Developmental Physiopathology Laboratory, UPMC Univ Paris 06, EA4053, Paris, France
Team 15, INSERM UMRS-893, CDR Saint-Antoine, Paris, France
Search for more papers by this authorSélim Aractingi
Developmental Physiopathology Laboratory, UPMC Univ Paris 06, EA4053, Paris, France
Team 15, INSERM UMRS-893, CDR Saint-Antoine, Paris, France
Department of Dermatology, AP-HP, Hôpital Tenon, Paris, France
Search for more papers by this authorSau Nguyen Huu
Developmental Physiopathology Laboratory, UPMC Univ Paris 06, EA4053, Paris, France
Team 15, INSERM UMRS-893, CDR Saint-Antoine, Paris, France
Search for more papers by this authorCorresponding Author
Kiarash Khosrotehrani
Developmental Physiopathology Laboratory, UPMC Univ Paris 06, EA4053, Paris, France
Team 15, INSERM UMRS-893, CDR Saint-Antoine, Paris, France
Department of Dermatology, AP-HP, Hôpital Tenon, Paris, France
Fax: +33156016458.
Department of Dermatology, AP-HP, Hôpital Tenon, 4 rue de la Chine, 75020 Paris, FranceSearch for more papers by this authorMichèle Oster
Developmental Physiopathology Laboratory, UPMC Univ Paris 06, EA4053, Paris, France
Team 15, INSERM UMRS-893, CDR Saint-Antoine, Paris, France
Search for more papers by this authorPhilippe Moguelet
Department of Pathology, AP-HP, Hôpital Tenon, Paris, France
Search for more papers by this authorMarie-Josée Espié
Developmental Physiopathology Laboratory, UPMC Univ Paris 06, EA4053, Paris, France
Team 15, INSERM UMRS-893, CDR Saint-Antoine, Paris, France
Search for more papers by this authorSélim Aractingi
Developmental Physiopathology Laboratory, UPMC Univ Paris 06, EA4053, Paris, France
Team 15, INSERM UMRS-893, CDR Saint-Antoine, Paris, France
Department of Dermatology, AP-HP, Hôpital Tenon, Paris, France
Search for more papers by this authorAbstract
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.
Supporting Information
Additional Supporting Information may be found in the online version of this article.
Filename | Description |
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IJC_23819_sm_suppinfoFigure.doc22 KB | Supplemental figure 1 : Phenotype of fetal cells in maternal skin tumour occurring after gestation. Chart representing the relative frequency of differentiation of the various fetal cells in endothelial (von willebrand +), hematopoietic (CD45+) or cytokeratin expressing cells. |
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References
- 1 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.
- 2 Nguyen Huu S,Dubernard G,Aractingi S,Khosrotehrani K. Feto-maternal cell trafficking: a transfer of pregnancy associated progenitor cells. Stem Cell Rev 2006; 2: 111–6.
- 3 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 USA 1996; 93: 705–8.
- 4 Guetta E,Gordon D,Simchen MJ,Goldman B,Barkai G Hematopoietic progenitor cells as targets for non-invasive prenatal diagnosis: detection of fetal CD34+ cells and assessment of post-delivery persistence in the maternal circulation. Blood Cells Mol Dis 2003; 30: 13–21.
- 5 Khosrotehrani K,Leduc M,Bachy V,Nguyen HS,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: 889–97.
- 6 O'Donoghue K,Chan J,De La FJ,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.
- 7 Srivatsa B,Srivatsa S,Johnson KL,Samura O,Lee SL,Bianchi DW. Microchimerism of presumed fetal origin in thyroid specimens from women: a case-control study. Lancet 2001; 358: 2034–8.
- 8 Khosrotehrani K,Johnson KL,Cha DH,Salomon RN,Bianchi DW. Transfer of fetal cells with multilineage potential to maternal tissue. JAMA 2004; 292: 75–80.
- 9 Khosrotehrani K,Reyes RR,Johnson KL,Freeman RB,Salomon RN,Peter I,Stroh H,Guegan 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.
- 10 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 USA 2007; 104: 1871–6.
- 11 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.
- 12 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.
- 13 Khosrotehrani K,Bianchi DW. Multi-lineage potential of fetal cells in maternal tissue: a legacy in reverse. J Cell Sci 2005; 118 (Part 8): 1559–63.
- 14 Barozzi P,Luppi M,Facchetti F,Mecucci C,Alu M,Sarid R,Rasini V,Ravazzini L,Rossi E,Festa S,Crescenzi B,Wolf DG, et al. Post-transplant Kaposi sarcoma originates from the seeding of donor-derived progenitors. Nat Med 2003; 9: 554–61.
- 15 Aractingi S,Kanitakis J,Euvrard S,Le Danff C,Peguillet I,Khosrotehrani K,Lantz O,Carosella ED. Skin carcinoma arising from donor cells in a kidney transplant recipient. Cancer Res 2005; 65: 1755–60.
- 16 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.
- 17 Cha D,Khosrotehrani K,Kim Y,Stroh H,Bianchi DW,Johnson KL. Cervical cancer and microchimerism. Obstet Gynecol 2003; 102: 774–81.
- 18 Okabe M,Ikawa M,Kominami K,Nakanishi T,Nishimune Y. ‘Green mice’ as a source of ubiquitous green cells. FEBS Lett 1997; 407: 313–9.
- 19 Yokota K,Gill TJ,III,Shinozuka H. Effects of oral versus topical administration of cyclosporine on phorbol ester promotion of murine epidermal carcinogenesis. Cancer Res 1989; 49: 4586–90.
- 20 Kruszewski FH,Conti CJ,DiGiovanni J Characterization of skin tumor promotion and progression by chrysarobin in SENCAR mice. Cancer Res 1987; 47: 3783–90.
- 21 Lesieur B,Vercambre M,Dubernard G,Khosrotehrani K,Uzan S,Aractingi S,Rouzier R. Risk of breast cancer related to pregnancy. J Gynecol Obstet Biol Reprod (Paris) 2008; 37: 77–81.
- 22 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.
- 23 Hugo H,Ackland ML,Blick T,Lawrence MG,Clements JA,Williams ED,Thompson EW. Epithelial–mesenchymal and mesenchymal–epithelial transitions in carcinoma progression. J Cell Physiol 2007; 213: 374–83.
- 24 Studeny M,Marini FC,Champlin RE,Zompetta C,Fidler IJ,Andreeff M. Bone marrow-derived mesenchymal stem cells as vehicles for interferon-beta delivery into tumors. Cancer Res 2002; 62: 3603–8.
- 25 Wu Y,Chen L,Scott PG,Tredget EE. Mesenchymal stem cells enhance wound healing through differentiation and angiogenesis. Stem Cells 2007; 25: 2648–59.
- 26 Reiners JJ,Jr,Singh KP. Susceptibility of 129/SvEv mice in two-stage carcinogenesis protocols to 12-O-tetradecanoylphorbol-13-acetate promotion. Carcinogenesis 1997; 18: 593–7.
- 27 Gadi VK,Malone KE,Guthrie KA,Porter PL,Nelson JL. Case-control study of fetal microchimerism and breast cancer. PLoS ONE 2008; 3: e1706.
- 28 Gadi VK,Nelson JL. Fetal microchimerism in women with breast cancer. Cancer Res 2007; 67: 9035–8.
- 29 Khosrotehrani K,Johnson KL,Guegan S,Stroh H,Bianchi DW. Natural history of fetal cell microchimerism during and following murine pregnancy. J Reprod Immunol 2005; 66: 1–12.