Human umbilical cord matrix mesenchymal stem cells suppress the growth of breast cancer by expression of tumor suppressor genes.
Human and rat umbilical cord matrix mesenchymal stem cells (UCMSC) possess the ability to control the growth of breast carcinoma cells. Comparative analyses of two types of UCMSC suggest that rat UCMSC-dependent growth regulation is significantly stronger than that of human UCMSC. Their different tumoricidal abilities were clarified by analyzing gene expression profiles in the two types of UCMSC. Microarray analysis revealed differential gene expression between untreated naïve UCMSC and those co-cultured with species-matched breast carcinoma cells. The analyses screened 17 differentially expressed genes that are commonly detected in both human and rat UCMSC. The comparison between the two sets of gene expression profiles identified two tumor suppressor genes, adipose-differentiation related protein (ADRP) and follistatin (FST), that were specifically up-regulated in rat UCMSC, but down-regulated in human UCMSC when they were co-cultured with the corresponding species' breast carcinoma cells. Over-expression of FST, but not ADRP, in human UCMSC enhanced their ability to suppress the growth of MDA-231 cells. The growth of MDA-231 cells was also significantly lower when they were cultured in medium conditioned with FST, but not ADRP over-expressing human UCMSC. In the breast carcinoma lung metastasis model generated with MDA-231 cells, systemic treatment with FST-over-expressing human UCMSC significantly attenuated the tumor burden. These results suggest that FST may play an important role in exhibiting stronger tumoricidal ability in rat UCMSC than human UCMSC and also implies that human UCMSC can be transformed into stronger tumoricidal cells by enhancing tumor suppressor gene expression.
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, 66506, United States of America.
Naomi
N
Ohta
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, 66506, United States of America.
Susumu
S
Ishiguro
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, 66506, United States of America.
Atsushi
A
Kawabata
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, 66506, United States of America.
Deepthi
D
Uppalapati
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, 66506, United States of America.
Marla
M
Pyle
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, 66506, United States of America.
Deryl
D
Troyer
Gene Expression and Genomics Unit, NIH Biomedical Research Center, National Institute on Aging, NIH, Baltimore, MD, 21224, United States of America.
Supriyo
S
De
Gene Expression and Genomics Unit, NIH Biomedical Research Center, National Institute on Aging, NIH, Baltimore, MD, 21224, United States of America.
Yongqing
Y
Zhang
Gene Expression and Genomics Unit, NIH Biomedical Research Center, National Institute on Aging, NIH, Baltimore, MD, 21224, United States of America.
Kevin G
KG
Becker
Department of Anatomy and Physiology, College of Veterinary Medicine, Kansas State University, Manhattan, 66506, United States of America.
Masaaki
M
Tamura
D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D001943:Breast Neoplasms / Q000235:genetics / Q000378:metabolism / Q000503:physiopathology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000502:physiology*; D002478:Cells, Cultured; D016000:Cluster Analysis; D005260:Female; D038681:Follistatin / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism; D059630:Mesenchymal Stem Cells / Q000502:physiology*; D020411:Oligonucleotide Array Sequence Analysis; D000070780:Perilipin-2; D051381:Rats; D060888:Real-Time Polymerase Chain Reaction
D038681:Follistatin; D008565:Membrane Proteins; C000602982:PLIN2 protein, human; D000070780:Perilipin-2; C000602984:Plin2 protein, rat