title: Human adipose tissue-derived stromal/stem cells promote migration and early metastasis of triple negative breast cancer xenografts.
abstract: BACKGROUND
  Fat grafting is used to restore breast defects after surgical resection of breast tumors. Supplementing fat grafts with adipose tissue-derived stromal/stem cells (ASCs) is proposed to improve the regenerative/restorative ability of the graft and retention. However, long term safety for ASC grafting in proximity of residual breast cancer cells is unknown. The objective of this study was to determine the impact of human ASCs derived from abdominal lipoaspirates of three donors, on a human breast cancer model that exhibits early metastasis.
  
  
  RESULTS
  Human MDA-MB-231 breast cancer cells represents "triple negative" breast cancer that exhibits early micrometastasis to multiple mouse organs [1]. Human ASCs were derived from abdominal adipose tissue from three healthy female donors. Indirect co-culture of MDA-MB-231 cells with ASCs, as well as direct co-culture demonstrated that ASCs had no effect on MDA-MB-231 growth. Indirect co-culture, and ASC conditioned medium (CM) stimulated migration of MDA-MB-231 cells. ASC/RFP cells from two donors co-injected with MDA-MB-231/GFP cells exhibited a donor effect for stimulation of primary tumor xenografts. Both ASC donors stimulated metastasis. ASC/RFP cells were viable, and integrated with MDA-MB-231/GFP cells in the tumor. Tumors from the co-injection group of one ASC donor exhibited elevated vimentin, matrix metalloproteinase-9 (MMP-9), IL-8, VEGF and microvessel density. The co-injection group exhibited visible metastases to the lung/liver and enlarged spleen not evident in mice injected with MDA-MB-231/GFP alone. Quantitation of the total area of GFP fluorescence and human chromosome 17 DNA in mouse organs, H&E stained paraffin sections and fluorescent microscopy confirmed multi-focal metastases to lung/liver/spleen in the co-injection group without evidence of ASC/RFP cells.
  
  
  CONCLUSIONS
  Human ASCs derived from abdominal lipoaspirates of two donors stimulated metastasis of MDA-MB-231 breast tumor xenografts to multiple mouse organs. MDA-MB-231 tumors co-injected with ASCs from one donor exhibited partial EMT, expression of MMP-9, and increased angiogenesis.
authors.affiliation: Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
authors.forename: Brian G
authors.initials: BG
authors.lastname: Rowan
authors.affiliation: Stem Cell Biology Laboratory, Pennington Biomedical Research Center, Louisiana State University, Baton Rouge, Louisiana, United States of America.
authors.forename: Jeffrey M
authors.initials: JM
authors.lastname: Gimble
authors.affiliation: Department of Otolaryngology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
authors.forename: Mei
authors.initials: M
authors.lastname: Sheng
authors.affiliation: Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
authors.forename: Muralidharan
authors.initials: M
authors.lastname: Anbalagan
authors.affiliation: Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
authors.forename: Ryan K
authors.initials: RK
authors.lastname: Jones
authors.affiliation: Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
authors.forename: Trivia P
authors.initials: TP
authors.lastname: Frazier
authors.affiliation: Department of Structural and Cellular Biology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
authors.forename: Majdouline
authors.initials: M
authors.lastname: Asher
authors.affiliation: Department of Otolaryngology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
authors.forename: Eduardo A
authors.initials: EA
authors.lastname: Lacayo
authors.affiliation: Department of Otolaryngology, Tulane University School of Medicine, New Orleans, Louisiana, United States of America.
authors.forename: Paul L
authors.initials: PL
authors.lastname: Friedlander
authors.affiliation: Gene Therapy Program, Louisiana State University Health Sciences Center, New Orleans, Louisiana, United States of America.
authors.forename: Robert
authors.initials: R
authors.lastname: Kutner
authors.affiliation: Department of Plastic Surgery, New York University Langone Medical Center, New York, New York, United States of America.
authors.forename: Ernest S
authors.initials: ES
authors.lastname: Chiu
mesh_terms: D000273:Adipose Tissue / Q000166:cytology*; D000818:Animals; D017077:Culture Media, Conditioned; D005260:Female; D006801:Humans; D016209:Interleukin-8 / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism; D051379:Mice; D013234:Stem Cells / Q000502:physiology*; D017154:Stromal Cells / Q000502:physiology*; D064726:Triple Negative Breast Neoplasms / Q000473:pathology*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D017077:Culture Media, Conditioned; D016209:Interleukin-8; D042461:Vascular Endothelial Growth Factor A; D020780:Matrix Metalloproteinase 9