title: Regenerative therapy and cancer: in vitro and in vivo studies of the interaction between adipose-derived stem cells and breast cancer cells from clinical isolates.
abstract: Adipose-derived stem cells (ASCs) have been proposed to stabilize autologous fat grafts for regenerative therapy, but their safety is unknown in the setting of reconstructive surgery after mastectomy. Both bone marrow mesenchymal stem cells (MSCs) and ASC have been shown to enhance tumorigenesis of established breast cancer cell lines, but primary patient material has not been tested. Here, we ask whether ASC promote the in vitro growth and in vivo tumorigenesis of metastatic breast cancer clinical isolates. Metastatic pleural effusion (MPE) cells were used for coculture experiments. ASC enhanced the proliferation of MPE cells in vitro (5.1-fold). For xenograft experiments (100 sorted cells/injection site), nonhematopoietic MPE cells were sorted into resting and active populations: CD90+ resting (low scatter, 2.1%≥2N DNA), CD90+ active (high scatter, 10.6%≥2N DNA), and CD90-. Resting CD90+ MPE cells were tumorigenic in 4/40 sites but growth was not augmented by ASC. Active CD90+ MPE cells were tumorigenic (17/40 sites) only when coinjected with ASC (p=0.0005, χ2 test). The multilineage potentiality and MSC-like immunophenotype of ASC were confirmed by flow cytometry, differentiation cultures, and immunostaining. The secretome profile of ASC resembled that reported for MSC, but included adipose-associated adipsin and the hormone leptin, shown to promote breast cancer growth. Our data indicate that ASC enhance the growth of active, but not resting tumor cells. Thus, reconstructive therapy utilizing ASC-augmented whole fat should be postponed until there is no evidence of active disease.
authors.affiliation: University of Pittsburgh Cancer Institute, Department of Medicine, University of Pittsburgh School of Medicine, Pittsburgh, Pennsylvania 15213, USA.
authors.forename: Ludovic
authors.initials: L
authors.lastname: Zimmerlin
authors.forename: Albert D
authors.initials: AD
authors.lastname: Donnenberg
authors.forename: J Peter
authors.initials: JP
authors.lastname: Rubin
authors.forename: Per
authors.initials: P
authors.lastname: Basse
authors.forename: Rodney J
authors.initials: RJ
authors.lastname: Landreneau
authors.forename: Vera S
authors.initials: VS
authors.lastname: Donnenberg
mesh_terms: D050156:Adipogenesis / Q000502:physiology; D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D001943:Breast Neoplasms / Q000628:therapy*; D002454:Cell Differentiation / Q000502:physiology; D049109:Cell Proliferation; D002478:Cells, Cultured; D020219:Chondrogenesis / Q000502:physiology; D005260:Female; D005434:Flow Cytometry; D005455:Fluorescent Antibody Technique; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D010012:Osteogenesis / Q000502:physiology; D033581:Stem Cell Transplantation / Q000379:methods*; D013234:Stem Cells / Q000166:cytology*; D014407:Tumor Cells, Cultured; D023041:Xenograft Model Antitumor Assays