Advertisement

Breast Cancer Research and Treatment

, Volume 156, Issue 1, pp 65–72 | Cite as

MSCs and inflammation: new insights into the potential association between ALCL and breast implants

  • M. Orciani
  • G. Sorgentoni
  • M. Torresetti
  • Roberto Di PrimioEmail author
  • G. Di Benedetto
Preclinical Study

Abstract

Possible association between anaplastic large cell lymphoma (ALCL) and breast implants has been suggested. In this context, formation of the periprosthetic capsule has been reported as a cause of inflammation, which plays a key role in tumor onset. Tumors take advantage of inflammation to influence and interfere with the host immune response by secreting multiple factors, and their onset and survival is in turn affected by the paracrine effects from mesenchymal stem cells (MSCs). In this study, we tried to clarify how inflammation can modify the immunobiology and the exerted paracrine effect of MSCs. MSCs derived from both inflamed (I-MSCs) and control (C-MSCs) tissues were isolated and co-cultured with an ALCL cell line. Proliferation rate and the expression of selected cytokines were tested. I-MSCs secrete higher levels of cytokine related to chronic inflammation than C-MSCs. After co-cultures with KI-JK cells, C- and I-MSCs show the same variation in the cytokine expression, with an increase of IL2, IL4, IL5, IL10, IL13, TNF-α, TGF-β, and G-CSF. Proliferation of ALCL cells was not influenced by co-cultures. Our results state that (i) inflamed microenvironment affects the immunobiology of MSCs modifying the profile of the expressed cytokines, and (ii) the paracrine effects exerted by MSCs on ALCL cells are not influenced by inflammation. Moreover, it seems that ALCL cells are able to manipulate MSCs’ immunoregulatory properties to evade the host immune control. Nevertheless, this ability is not associated with inflammation and the question about BIA-ALCL is not proved by our experiments.

Keywords

ALCL MSCs Breast implants Paracrine effects 

Notes

Acknowledgments

This work was supported by the Grants FIRB-RBAP1153LS_004 and PRIN 201098WFZ2_006 from Ministero dell’Istruzione, dell’Università e della Ricerca, Rome, Italy.

Compliance with ethical standards

Conflict of interest

None of the authors have a financial interest in any of the products, devices, or drugs mentioned in this manuscript.

Ethical approval

The study and the patient enrollment were approved by the Marche Polytechnic University Ethical Commitee and were conducted in accordance with the Declaration of Helsinki.

References

  1. 1.
    Hu T, Li LF, Shen J, Zhang L, Cho CH (2015) Chronic inflammation and colorectal cancer: the role of vascular endothelial growth factor. Curr Pharm Des 21:2960–2967CrossRefPubMedGoogle Scholar
  2. 2.
    Raposo TP, Beirão BC, Pang LY, Queiroga FL, Argyle DJ (2015) Inflammation and cancer: till death tears them apart. Vet J 205:161–174CrossRefPubMedGoogle Scholar
  3. 3.
    Chai EZ, Siveen KS, Shanmugam MK, Arfuso F, Sethi G (2015) Analysis of the intricate relationship between chronic inflammation and cancer. Biochem J 468:1–15CrossRefPubMedGoogle Scholar
  4. 4.
    Orciani M, Lazzarini R, Scartozzi M, Bolletta E, Mattioli-Belmonte M, Scalise A, Di Benedetto G, Di Primio R (2013) The response of breast cancer cells to mesenchymal stem cells: a possible role of inflammation by breast implants. Plast Reconstr Surg 132:899e–910eCrossRefPubMedGoogle Scholar
  5. 5.
    Orciani M, Bolletta E, Campanati A, Di Benedetto G, Di Primio R (2014) The response of breast cancer cells to mesenchymal stem cells: a possible role of inflammation by breast implants. Plast Reconstr Surg 134:994e–996eCrossRefPubMedGoogle Scholar
  6. 6.
    Mariotti C, Lazzarini R, Nicolai M, Saitta A, Orsini E, Orciani M, Di Primio R (2015) Comparative study between amniotic-fluid mesenchymal stem cells and retinal pigmented epithelium (RPE) stem cells ability to differentiate towards RPE cells. Cell Tissue Res 362:21–31CrossRefPubMedGoogle Scholar
  7. 7.
    Orciani M, Davis S, Appolloni G, Lazzarini R, Mattioli-Belmonte M, Ricciuti RA, Boscaro M, Di Primio R, Arnaldi G (2015) Isolation and characterization of progenitor mesenchymal cells in human pituitary tumors. Cancer Gene Ther 22:9–16CrossRefPubMedGoogle Scholar
  8. 8.
    Orciani M, Campanati A, Salvolini E, Lucarini G, Di Benedetto G, Offidani A, Di Primio R (2011) The mesenchymal stem cell profile in psoriasis. Br J Dermatol 165:585–592CrossRefPubMedGoogle Scholar
  9. 9.
    Orciani M, Morabito C, Emanuelli M, Guarnieri S, Sartini D, Giannubilo SR, Di Primio R, Tranquilli AL, Mariggiò MA (2011) Neurogenic potential of mesenchymal-like stem cells from human amniotic fluid: the influence of extracellular growth factors. J Biol Regul Homeost Agents 25:115–130PubMedGoogle Scholar
  10. 10.
    Orciani M, Mariggiò MA, Morabito C, Di Benedetto G, Di Primio R (2010) Functional characterization of calcium-signaling pathways of human skin-derived mesenchymal stem cells. Skin Pharmacol Physiol. 23:124–132CrossRefPubMedGoogle Scholar
  11. 11.
    Fierro FA, Sierralta WD, Epuñan MJ, Minguell JJ (2004) Marrow-derived mesenchymal stem cells: role in epithelial tumor cell determination. Clin Exp Metastasis 21:313–319CrossRefPubMedGoogle Scholar
  12. 12.
    Sasser AK, Mundy BL, Smith KM, Studebaker AW, Axel AE, Haidet AM, Fernandez SA, Hall BM (2007) Human bone marrow stromal cells enhance breast cancer cell growth rates in a cell line-dependent manner when evaluated in 3D tumor environments. Cancer Lett 254:255–264CrossRefPubMedGoogle Scholar
  13. 13.
    Klopp AH, Gupta A, Spaeth E, Andreeff M, Marini F 3rd (2011) Concise review: dissecting a discrepancy in the literature: do mesenchymal stem cells support or suppress tumor growth? Stem Cells 29:11–19 (Review) CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Lee YS, Filie A, Arthur D, Fojo AT, Jaffe ES (2015) Breast-implant-associated anaplastic large cell lymphoma in a patient with Li-Fraumeni syndrome. Histopathology 67:925–927CrossRefPubMedGoogle Scholar
  15. 15.
    Locke MB, Lofts J (2015) Variable presentation of anaplastic large-cell lymphoma in patients with breast implants. ANZ J Surg 1:2–6Google Scholar
  16. 16.
    Hwang MJ, Brown H, Murrin R, Momtahan N, Sterne GD (2015) Breast implant-associated anaplastic large cell lymphoma: a case report and literature review. Aesthetic Plast Surg 39:391–395CrossRefPubMedGoogle Scholar
  17. 17.
    Kim B, Predmore ZS, Mattke S, van Busum K, Gidengil CA (2015) Breast implant-associated anaplastic large cell lymphoma: updated results from a structured expert consultation process. Plast Reconstr Surg Glob Open 3:e296CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Peters W (2014) Update on anaplastic large cell lymphoma in women with breast implants. Can J Plast Surg 22:267–269Google Scholar
  19. 19.
    Gidengil CA, Predmore Z, Mattke S, van Busum K, Kim B (2015) Breast implant-associated anaplastic large cell lymphoma: a systematic review. Plast Reconstr Surg 135:713–720CrossRefPubMedGoogle Scholar
  20. 20.
    Brody GS, Deapen D, Taylor CR, Pinter-Brown L, House-Lightner SR, Andersen JS, Carlson G, Lechner MG, Epstein AL (2015) Anaplastic large cell lymphoma occurring in women with breast implants: analysis of 173 cases. Plast Reconstr Surg 135:695–705CrossRefPubMedGoogle Scholar
  21. 21.
    Adrada BE, Miranda RN, Rauch GM, Arribas E, Kanagal-Shamanna R, Clemens MW, Fanale M, Haideri N, Mustafa E, Larrinaga J, Reisman NR, Jaso J, You MJ, Young KH, Medeiros LJ, Yang W (2014) Breast implant-associated anaplastic large cell lymphoma: sensitivity, specificity, and findings of imaging studies in 44 patients. Breast Cancer Res Treat 147:1–14CrossRefPubMedGoogle Scholar
  22. 22.
    Xu J, Wei S (2014) Breast implant-associated anaplastic large cell lymphoma: review of a distinct clinicopathologic entity. Arch Pathol Lab Med 138:842–846CrossRefPubMedGoogle Scholar
  23. 23.
    Miranda RN, Aladily TN, Prince HM, Kanagal-Shamanna R, de Jong D, Fayad LE et al (2014) Breast implant-associated anaplastic large-cell lymphoma: long-term follow-up of 60 patients. J Clin Oncol 32:114–120CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Campanati A, Orciani M, Consales V, Lazzarini R, Ganzetti G, Di Benedetto G, Di Primio R, Offidani A (2014) Characterization and profiling of immunomodulatory genes in resident mesenchymal stem cells reflect the Th1-Th17/Th2 imbalance of psoriasis. Arch Dermatol Res 306:915–920CrossRefPubMedGoogle Scholar
  25. 25.
    Campanati A, Orciani M, Gorbi S, Regoli F, Di Primio R, Offidani A (2012) Effect of biologic therapies targeting tumour necrosis factor-α on cutaneous mesenchymal stem cells in psoriasis. Br J Dermatol 167:68–76CrossRefPubMedGoogle Scholar
  26. 26.
    Orciani M, Di Primio R (2013) Skin-derived mesenchymal stem cells: isolation, culture, and characterization. Methods Mol Biol 989:275–283CrossRefPubMedGoogle Scholar
  27. 27.
    Orciani M, Gorbi S, Benedetti M, Di Benedetto G, Mattioli-Belmonte M, Regoli F, Di Primio R (2010) Oxidative stress defense in human-skin-derived mesenchymal stem cells versus human keratinocytes: different mechanisms of protection and cell selection. Free Radic Biol Med 49:830–838CrossRefPubMedGoogle Scholar
  28. 28.
    Kim B, Roth C, Chung KC, Young VL, van Busum K, Schnyer C, Mattke S (2011) Anaplastic large cell lymphoma and breast implants: a systematic review. Plast Reconstr Surg 127:2141–2150CrossRefPubMedGoogle Scholar
  29. 29.
    Lazzarini R, Olivieri F, Ferretti C, Mattioli-Belmonte M, Di Primio R, Orciani M (2014) mRNAs and miRNAs profiling of mesenchymal stem cells derived from amniotic fluid and skin: the double face of the coin. Cell Tissue Res 355:121–130CrossRefPubMedGoogle Scholar
  30. 30.
    Coussens LM, Werb Z (2002) Inflammation and cancer. Nature 420:860–867CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Elinav E, Nowarski R, Thaiss CA, Hu B, Jin C, Flavell RA (2013) Inflammation-induced cancer: crosstalk between tumours, immune cells and microorganisms. Nat Rev Cancer 13:759–771CrossRefPubMedGoogle Scholar
  32. 32.
    Balkwill F, Mantovani A (2001) Inflammation and cancer: back to Virchow? Lancet 357:539–545CrossRefPubMedGoogle Scholar
  33. 33.
    Ono M (2008) Molecular links between tumor angiogenesis and inflammation: inflammatory stimuli of macrophages and cancer cells as targets for therapeutic strategy. Cancer Sci 99:1501–1506CrossRefPubMedGoogle Scholar
  34. 34.
    Balkwill F, Charles KA, Mantovani A (2005) Smoldering and polarized inflammation in the initiation and promotion of malignant disease. Cancer Cell 7:211–217CrossRefPubMedGoogle Scholar
  35. 35.
    de Visser KE, Coussens LM (2006) The inflammatory tumor microenvironment and its impact on cancer development. Contrib Microbiol 13:118–137CrossRefPubMedGoogle Scholar
  36. 36.
    Motz GT, Coukos G (2013) Deciphering and reversing tumor immune suppression. Immunity 39:61–73CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Aggarwal BB (2009) Inflammation, a silent killer in cancer is not so silent! Curr Opin Pharmacol 9:347–350CrossRefPubMedGoogle Scholar
  38. 38.
    Aggarwal BB, Gehlot P (2009) Inflammation and cancer: how friendly is the relationship for cancer patients? Curr Opin Pharmacol 9:351–369CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    Grivennikov SI, Greten FR, Karin M (2010) Immunity, inflammation, and cancer. Cell 140:883–899CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Hu H, Jacombs A, Vickery K, Merten SL, Pennington DG, Deva AK (2015) Chronic biofilm infection in breast implants is associated with an increased T-cell lymphocytic infiltrate: implications for breast implant-associated lymphoma. Plast Reconstr Surg 135:319–329CrossRefPubMedGoogle Scholar
  41. 41.
    George EV, Pharm J, Houston C, Al-Quran S, Brian G, Dong H, Hai W, Reeves W, Yang LJ (2013) Breast implant-associated ALK-negative anaplastic large cell lymphoma: a case report and discussion of possible pathogenesis. Int J Clin Exp Pathol 6:1631–1642PubMedPubMedCentralGoogle Scholar
  42. 42.
    Kopf M, Baumann H, Freer G, Freudenberg M, Lamers M, Kishimoto T, Zinkernagel R, Bleuthmann H, Kohler G (1994) Impaired immune and acute-phase responses in interleukin-6-deficient mice. Nature 368:339–342CrossRefPubMedGoogle Scholar
  43. 43.
    Romani L, Mencacci A, Cenci E, Spaccapelo R, Toniatti C, Puccetti P, Bistoni F, Poli V (1996) Impaired neutrophil response and CD41 T helper cell 1 development in interleukin-6-deficient mice infected with Candida albicans. J Exp Med 183:1345–1355CrossRefPubMedGoogle Scholar
  44. 44.
    Ruzek MC, Miller AH, Opal SM, Pearce BD, Biron CA (1997) Characterization of early cytokine responses and an interleukin-6-dependent pathway of endogenous glucocorticoid induction during murine cytomegalovirus infection. J Exp Med 185:1185–1192CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    Kaplanski G, Marin V, Montero-Julian F, Mantovani A, Farnarier C (2003) IL-6: a regulator of the transition from neutrophil to monocyte recruitment during inflammation. Trends Immunol 24:25–29CrossRefPubMedGoogle Scholar
  46. 46.
    Lin WW, Karin M (2007) A cytokine-mediated link between innate immunity, inflammation, and cancer. J Clin Invest 117:1175–1183CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Smyth MJ, Dunn GP, Schreiber RD (2006) Cancer immunosurveillance and immunoediting: the roles of immunity in suppressing tumor development and shaping tumor immunogenicity. Adv Immunol 90:1–50CrossRefPubMedGoogle Scholar
  48. 48.
    Bui JD, Schreiber RD (2007) Cancer immunosurveillance, immunoediting and inflammation: independent or interdependent processes? Curr Opin Immunol 19:203–208CrossRefPubMedGoogle Scholar
  49. 49.
    Teng MW, Swann JB, Koebel CM, Schreiber RD, Smyth MJ (2008) Immune-mediated dormancy: an equilibrium with cancer. J Leukoc Biol 84:988–993CrossRefPubMedGoogle Scholar
  50. 50.
    Swann JB, Vesely MD, Silva A, Sharkey J, Akira S, Schreiber RD, Smyth MJ (2008) Demonstration of inflammation-induced cancer and cancer immunoediting during primary tumorigenesis. Proc Natl Acad Sci USA 105:652–656CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Swann JB, Smyth MJ (2007) Immune surveillance of tumors. J Clin Invest 117:1137–1146CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Siegel G, Schäfer R, Dazzi F (2009) The immunosuppressive properties of mesenchymal stem cells. Transplantation 87:S45–S49CrossRefPubMedGoogle Scholar
  53. 53.
    Lu H, Ouyang W, Huang C (2006) Inflammation, a key event in cancer development. Mol Cancer Res 4:221–233CrossRefPubMedGoogle Scholar
  54. 54.
    Steinbrink K, Jonuleit H, Müller G, Schuler G, Knop J, Enk AH (1999) Interleukin-10-treated human dendritic cells induce a melanoma-antigen-specific anergy in CD8+ T cells resulting in a failure to lyse tumor cells. Blood 93:1634–1642PubMedGoogle Scholar
  55. 55.
    Bayne L, Beatty GL, Jhala N, Clark CE, Rhim AD, Stanger BZ, Vonderheide RH (2012) Tumor-derived granulocyte-macrophage colony-stimulating factor regulates myeloid inflammation and T cell immunity in pancreatic cancer. Cancer Cell 21:822–835CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Gabrilovich DI, Nagaraj S (2009) Myeloid-derived suppressor cells as regulators of the immune system. Nat Rev Immunol 9:162–174CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer Science+Business Media New York 2016

Authors and Affiliations

  • M. Orciani
    • 1
  • G. Sorgentoni
    • 1
  • M. Torresetti
    • 2
  • Roberto Di Primio
    • 1
    Email author
  • G. Di Benedetto
    • 2
  1. 1.Department of Clinical and Molecular Sciences – HistologyUniversità Politecnica delle MarcheAnconaItaly
  2. 2.Department of Experimental and Clinical Medicine – Clinic of Plastic and Reconstructive SurgeryUniversità Politecnica delle MarcheAnconaItaly

Personalised recommendations