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Trafficking of Cells from Adipose Tissue to Tumor Microenvironment

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Adipose Tissue and Cancer

Abstract

Similar to neoplasia, the human white adipose tissue (WAT) shows in vivo a robust angiogenic switch when the growth rate exceeds a given expansion threshold. Also, antiangiogenic drugs have been found to inhibit WAT development in postnatal mice. Human WAT is very rich in CD45−CD34+ progenitors that express high levels of angiogenesis-related genes and can generate in culture endothelial cells and tubes as efficiently as mesenchymal cells. Compared to the bone marrow, WAT contains >250 times more CD45−CD34+ progenitors with endothelial differentiation potential. The coinjection of human WAT-derived CD45−CD34+ progenitors from lipotransfer procedures contributed to tumor vascularization and significantly increased tumor growth and metastases in several orthotopic models of human breast cancer in immunodeficient NSG mice. These data nicely complement the recent observation from the Kolonin laboratory that in mouse models WAT cells are mobilized and recruited by experimental tumors to promote cancer progression. Autologous lipotransfer for tissue/organ reconstruction is used in patients who had surgical removal of breast and other types of cancer. We have recently reported a study of 321 consecutive patients operated for primary breast cancer who subsequently underwent a lipotransfer procedure, compared with two matched patients with similar characteristics who did not undergo lipotransfer. In this study, the lipotransfer group exhibited a higher risk of local events compared to the controls when the analysis was limited to intraepithelial neoplasia. A second data revision after prolonged follow-up confirmed this significant difference. The dissection of the different roles of purified populations of WAT-derived progenitors and mature cells seems urgent to clarify which WAT cell populations can be used safely for tissue/organ reconstruction in cancer patients.

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References

  1. Stoll BR, Migliorini C, Kadambi A, Munn LL, Jain RK. A mathematical model of the contribution of endothelial progenitor cells to angiogenesis in tumors: implications for antiangiogenic therapy. Blood. 2003;102:2555–61.

    Article  PubMed  CAS  Google Scholar 

  2. Peters BA, Diaz LA, Polyak K, et al. Contribution of bone marrow-derived endothelial cells to human tumor vasculature. Nat Med. 2005;11:261–2.

    Article  PubMed  CAS  Google Scholar 

  3. Ribatti D, Nico B, Crivellato E, Vacca A. Endothelial progenitor cells in health and disease. Histol Histopathol. 2005;20:1351–8.

    PubMed  CAS  Google Scholar 

  4. Bertolini F, Shaked Y, Mancuso P, Kerbel RS. The multifaceted circulating endothelial cell in cancer: towards marker and target identification. Nat Rev Cancer. 2006;6:835–45.

    Article  PubMed  CAS  Google Scholar 

  5. Kaplan RN, Rafii S, Lyden D. Preparing the “soil”. The premetastatic niche. Cancer Res. 2006;66:11089–93.

    Article  PubMed  CAS  Google Scholar 

  6. De Palma M, Naldini L. Role of hematopoietic cells and endothelial progenitors in tumor angiogenesis. Biochim Biophys Acta. 2006;1766:159–66.

    PubMed  Google Scholar 

  7. Seandel M, Butler J, Lyden D, Rafii S. A catalytic role for proangiogenic marrow-derived cells in tumor neovascularisation. Cancer Cell. 2008;13:181–3.

    Article  PubMed  CAS  Google Scholar 

  8. Purhonen S, Palm J, Rossi D, et al. Bone marrow-derived circulating endothelial precursors do not contribute to vascular endothelium and are not needed for tumor growth. Proc Natl Acad Sci USA. 2008;105:6620–5.

    Article  PubMed  CAS  Google Scholar 

  9. Hirschi KK, Ingram DA, Yoder MC. Assessing identity, phenotype, and fate of endothelial progenitor cells. Arterioscler Thromb Vasc Biol. 2008;28:1584–95.

    Article  PubMed  CAS  Google Scholar 

  10. Yoder MC, Ingram DA. The definition of EPCs and other bone marrow cells contributing to neoangiogenesis and tumor growth: is there common ground for understanding the roles of numerous marrow-derived cells in the neoangiogenic process? Biochim Biophys Acta. 2009;1796:50–4.

    PubMed  CAS  Google Scholar 

  11. Shaked Y, Voest EE. Bone marrow derived cells in tumor angiogenesis and growth: are they the good, the bad or the evil? Biochim Biophys Acta. 2009;1796:1–4.

    PubMed  CAS  Google Scholar 

  12. Bertolini F, Mancuso P, Braidotti P, Shaked Y, Kerbel RS. The multiple personality disorder phenotype(s) of circulating endothelial cells in cancer. Biochim Biophys Acta. 2009;1796:27–32.

    PubMed  CAS  Google Scholar 

  13. Grenier G, Scimè A, Le Grand F, et al. Resident endothelial precursors in muscle, adipose, and dermis contribute to postnatal vasculogenesis. Stem Cells. 2007;25:3101–10.

    Article  PubMed  CAS  Google Scholar 

  14. Kraman M, Bambrough PJ, Arnold JN, et al. Suppression of antitumor immunity by stromal cells expressing fibroblast activation protein-alpha. Science. 2010;330:827–30.

    Article  PubMed  CAS  Google Scholar 

  15. Lohsiriwat V, Curigliano G, Rietjens M, Goldhirsch A, Petit YV. Autologous fat transplantation in patients with breast cancer: “silencing” or “fueling” cancer recurrence? Breast. 2011;20:351–7.

    Article  PubMed  Google Scholar 

  16. Petit JY, Clough K, Sarfati I, Lohsiriwat V, de Lorenzi F, Rietjens M. Lipotransfer in breast cancer patients: from surgical technique to oncologic point of view. Plast Reconstr Surg. 2010;126:262–3.

    Article  Google Scholar 

  17. Sengenès C, Lolmède K, Zakaroff-Girard A, Busse R, Bouloumié A. Preadipocytes in the human subcutaneous adipose tissue display distinct features from the adult mesenchymal and hematopoietic stem cells. J Cell Physiol. 2005;205:114–22.

    Article  PubMed  Google Scholar 

  18. Mancuso P, Antoniotti P, Quarna J, et al. Validation of a standardized method for enumerating circulating endothelial cells and progenitors: flow cytometry and molecular and ultrastructural analyses. Clin Cancer Res. 2009;15:267–73.

    Article  PubMed  CAS  Google Scholar 

  19. Mancuso P, Martin-Padura I, Calleri A, et al. Circulating perivascular progenitors, a target of PDGFR inhibition. Int J Cancer. 2011;129:1344–50.

    Article  PubMed  CAS  Google Scholar 

  20. Rabascio C, Muratori E, Mancuso P, et al. Assessing tumor angiogenesis: increased circulating VE-cadherin RNA in patients with cancer indicates viability of circulating endothelial cells. Cancer Res. 2004;15:4373–7.

    Article  Google Scholar 

  21. Corada M, Liao F, Lindgren M, et al. Monoclonal antibodies directed to different regions of vascular endothelial cadherin extracellular domain affect adhesion and clustering of the protein and modulate endothelial permeability. Blood. 2001;97:1679–84.

    Article  PubMed  CAS  Google Scholar 

  22. Cicalese A, Bonizzi G, Pasi CE, et al. The tumor suppressor p53 regulates polarity of self-renewing divisions in mammary stem cells. Cell. 2009;138:1083–95.

    Article  PubMed  CAS  Google Scholar 

  23. Shultz LD, Ishikawa F, Greiner DL. Humanized mice in translational biomedical research. Nat Rev Immunol. 2007;7:118–30.

    Article  PubMed  CAS  Google Scholar 

  24. Agliano A, Martin-Padura I, Marighetti P, et al. Human acute leukemia cells injected in NOD/LtSz-scid/IL-2Rgamma null mice generate a faster and more efficient disease compared to other NOD/scid-related strains. Int J Cancer. 2008;123:2222–7.

    Article  PubMed  CAS  Google Scholar 

  25. Napoli C, Martin-Padura I, De Nigris F, et al. Deletion of the p66Shc longevity gene reduces systemic and tissue oxidative stress, vascular cell apoptosis, and early atherogenesis in mice fed a high-fat diet. Proc Natl Acad Sci USA. 2003;100:2112–6.

    Article  PubMed  CAS  Google Scholar 

  26. Martin-Padura I, Gregato G, Marighetti P, et al. The white adipose tissue used in lipotransfer procedures is a rich reservoir of CD34+ progenitors able to promote cancer progression. Cancer Res. 2012;72:325–34.

    Article  PubMed  CAS  Google Scholar 

  27. Cao L, Liu X, Lin EJ, et al. Environmental and genetic activation of a brain-adipocyte BDNF/leptin axis causes cancer remission and inhibition. Cell. 2010;142:52–64.

    Article  PubMed  CAS  Google Scholar 

  28. Zimmerlin L, Donnenberg VS, Pfeifer ME, et al. Stromal vascular progenitors in adult human adipose tissue. Cytometry A. 2010;77:22–30.

    PubMed  Google Scholar 

  29. Ingram DA, Mead LE, Tanaka H, et al. Identification of a novel hierarchy of endothelial progenitor cells using human peripheral and umbilical cord blood. Blood. 2004;104:2752–60.

    Article  PubMed  CAS  Google Scholar 

  30. Ingram DA, Mead LE, Moore DB, Woodard W, Fenoglio A, Yoder MC. Vessel wall-derived endothelial cells rapidly proliferate because they contain a complete hierarchy of endothelial progenitor cells. Blood. 2005;105:2783–6.

    Article  PubMed  CAS  Google Scholar 

  31. Case J, Mead LE, Bessler WK, et al. Human CD34+AC133+VEGFR-2+ cells are not endothelial progenitor cells but distinct, primitive hematopoietic progenitors. Exp Hematol. 2007;35:1109–18.

    Article  PubMed  CAS  Google Scholar 

  32. Estes ML, Mund JA, Ingram DA, Case J. Identification of endothelial cells and progenitor cell subsets in human peripheral blood. Curr Protoc Cytom. 2010;9:1–11.

    Google Scholar 

  33. Klopp AH, Gupta A, Spaeth E, Andreeff M, Marini 3rd F. Concise review: dissecting a discrepancy in the literature: do mesenchymal stem cells support or suppress tumor growth? Stem Cells. 2011;29:11–9.

    Article  PubMed  CAS  Google Scholar 

  34. Zhang Y, Daquinaq A, Traktuev DO, et al. White adipose tissue cells are recruited by experimental tumors and promote cancer progression in mouse models. Cancer Res. 2009;69:5259–66.

    Article  PubMed  CAS  Google Scholar 

  35. Harris HR, Willet WC, Terry KL, Michels KB. Body fat distribution and risk of premenopausal breast cancer in the Nurses’ Health Study II. J Natl Cancer Inst. 2011;103:273–8.

    Article  PubMed  Google Scholar 

  36. Sinicrope FA, Dannenberg AJ. Obesity and breast cancer prognosis: weight of the evidence. J Clin Oncol. 2011;29:4–7.

    Article  PubMed  Google Scholar 

  37. Bellows CF, Zhang Y, Simmons PJ, Khalsa AS, Kolonin MG. Influence of BMI on level of circulating progenitor cells. Obesity (Silver Spring). 2011;19:1722–6.

    Article  Google Scholar 

  38. Petit JY, Botteri E, Lohsiriwat V, et al. Locoregional recurrence risk after lipotransfer in breast cancer patients. Ann Oncol. 2012;23:582–8.

    Article  PubMed  CAS  Google Scholar 

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Acknowledgment

Supported in part by AIRC (Associazione Italiana per la Ricerca sul Cancro), Fondazione Umberto Veronesi, ISS (Istituto Superiore di Sanità), and Ministero della Salute. F. Bertolini is a scholar of the US National Blood Foundation.

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Correspondence to Francesco Bertolini M.D., Ph.D. .

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Martin-Padura, I., Mancuso, P., Bertolini, F. (2013). Trafficking of Cells from Adipose Tissue to Tumor Microenvironment. In: Kolonin, M. (eds) Adipose Tissue and Cancer. Springer, New York, NY. https://doi.org/10.1007/978-1-4614-7660-3_8

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