MSCs and inflammation: new insights into the potential association between ALCL and breast implants
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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.
KeywordsALCL MSCs Breast implants Paracrine effects
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.
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.
- 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
- 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
- 18.Peters W (2014) Update on anaplastic large cell lymphoma in women with breast implants. Can J Plast Surg 22:267–269Google Scholar
- 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
- 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
- 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