title: Human adipose stem cell differentiation is highly affected by cancer cells both in vitro and in vivo: implication for autologous fat grafting.
abstract: Recent studies showed that mesenchymal stem cells derived from adipose tissue can promote tumour progression, raising some concerns regarding their use in regenerative medicine. In this context, we co-cultured either SAOS2 osteosarcoma or MCF7 breast cancer cells with human adipose stem cells (hASCs), in order to evaluate potential effects of cancer cells on hASCs differentiation, in vitro and in vivo. In this study we observed that both SAOS2 and MCF7 cell lines induced an increase in hASCs proliferation, compared to hASCs alone, but, surprisingly, neither changes in the expression of CD90, CD29, CD324 and vimentin, nor variations in the Twist and Slug mRNAs were detectable. Noteworthy, SAOS2 and MCF7 cells induced in hASCs an upregulation of CD34 expression and stemness genes, including OCT3/4, Nanog, Sox2 and leptin, and a decrease in angiogenic factors, including CD31, PDGFα, PDGFRα, PDGFRβ and VEGF. SMAD and pSMAD2/3 increased only in hASCs alone. After 21 days of co-culture, hASCs differentiated both in adipocytes and endothelial cells. Moreover, co-injection of MCF7 cells with hASCs led to the formation of a highly vascularized tumour. Taken together our findings suggest that mesenchymal stem cells, under tumour cell induction, do not differentiate in vitro or facilitate the angiogenesis of the tumour in vivo, thus opening interesting new scenarios in the relationship between cancer and stem cells. These findings may also lead to greater caution, when managing autologous fat grafts in cancer patients.
authors.affiliation: Dipartimento di Medicina Sperimentale, Sezione di Biotecnologie, Istologia Medica e Biologia Molecolare, Seconda Università degli Studi di Napoli, Napoli, Italy.
authors.forename: Francesca
authors.initials: F
authors.lastname: Paino
authors.affiliation: Dipartimento di Medicina Sperimentale, Sezione di Biotecnologie, Istologia Medica e Biologia Molecolare, Seconda Università degli Studi di Napoli, Napoli, Italy.
authors.forename: Marcella
authors.initials: M
authors.lastname: La Noce
authors.affiliation: Dipartimento di Medicina Sperimentale, Stabulario, Seconda Università degli Studi di Napoli, Napoli, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Di Nucci
authors.affiliation: Dipartimento Multidisciplinare di Specialità Medico-Chirurgiche ed Odontoiatriche, Seconda Università degli Studi di Napoli, Napoli, Italy.
authors.forename: Giovanni Francesco
authors.initials: GF
authors.lastname: Nicoletti
authors.affiliation: Dipartimento Multidisciplinare di Specialità Medico-Chirurgiche ed Odontoiatriche, Seconda Università degli Studi di Napoli, Napoli, Italy.
authors.forename: Rosa
authors.initials: R
authors.lastname: Salzillo
authors.affiliation: Dipartimento Multidisciplinare di Specialità Medico-Chirurgiche ed Odontoiatriche, Seconda Università degli Studi di Napoli, Napoli, Italy.
authors.forename: Alfredo
authors.initials: A
authors.lastname: De Rosa
authors.affiliation: Dipartimento Multidisciplinare di Specialità Medico-Chirurgiche ed Odontoiatriche, Seconda Università degli Studi di Napoli, Napoli, Italy.
authors.forename: Giuseppe Andrea
authors.initials: GA
authors.lastname: Ferraro
authors.affiliation: Dipartimento di Medicina Sperimentale, Sezione di Biotecnologie, Istologia Medica e Biologia Molecolare, Seconda Università degli Studi di Napoli, Napoli, Italy.
authors.forename: Gianpaolo
authors.initials: G
authors.lastname: Papaccio
authors.affiliation: Dipartimento di Medicina Sperimentale, Sezione di Biotecnologie, Istologia Medica e Biologia Molecolare, Seconda Università degli Studi di Napoli, Napoli, Italy.
authors.forename: Vincenzo
authors.initials: V
authors.lastname: Desiderio
authors.affiliation: Dipartimento di Medicina Sperimentale, Sezione di Biotecnologie, Istologia Medica e Biologia Molecolare, Seconda Università degli Studi di Napoli, Napoli, Italy.
authors.forename: Virginia
authors.initials: V
authors.lastname: Tirino
mesh_terms: D017667:Adipocytes / Q000166:cytology / Q000378:metabolism; D000818:Animals; D002454:Cell Differentiation / Q000187:drug effects / Q000235:genetics*; D049109:Cell Proliferation / Q000235:genetics*; D018920:Coculture Techniques; D042783:Endothelial Cells / Q000166:cytology; D005434:Flow Cytometry; D006801:Humans; D061986:MCF-7 Cells; D059630:Mesenchymal Stem Cells / Q000166:cytology* / Q000378:metabolism; D051379:Mice; D009389:Neovascularization, Pathologic / Q000235:genetics / Q000378:metabolism* / Q000473:pathology