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Malignant transformation of multipotent muscle-derived cells by concurrent differentiation signals

Pollett, JB and Corsi, KA and Weiss, KR and Cooper, GM and Barry, DA and Gharaibeh, B and Huard, J (2007) Malignant transformation of multipotent muscle-derived cells by concurrent differentiation signals. Stem Cells, 25 (9). 2302 - 2311. ISSN 1066-5099

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Abstract

Recent studies have shown that germ-line determination occurs early in development and that extracellular signaling can alter this fate. This denial of a cell's fate by counteracting its intrinsic signaling pathways through extrinsic stimulation is believed to be associated with oncogenesis. Using specific populations of multipotent skeletal muscle-derived stem cells (MDSCs), we have been able to generate tumors by subjecting cells with specific lineage predilections to concomitant differentiation signals. More specifically, when a stem cell that had a predilection toward osteogenesis was implanted into a skeletal muscle, tumors formed in 25% of implanted mice. When cells predilected to undergo myogenesis were pretreated with bone morphogenetic protein 4 (BMP4) for 4 days prior to implantation, they formed tumors in 25% of mice. These same myogenic predilected cells, when transduced to express BMP4 and implanted into either a long-bone or cranial defect, formed bone, but they formed tumors in 100% of mice when implanted into the skeletal muscle. The tumors generated in this latter study were serially transplantable as long as they retained BMP4 expression. Furthermore, when we impeded the ability of the cells to undergo myogenic differentiation using small interfering RNA to the myogenic regulator MyoD1, we stopped transformation. Based on our findings, we postulate that specific MDSC populations can undergo concomitant signal-induced transformation and that the initial stages of transformation may be due to changes in the balance between the inherent nature of the cell and extrinsic signaling pathways. This theory represents a potential link between somatic stem cells and cancer and suggests an involvement of the niche/environment in transformation. ©AlphaMed Press.


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Details

Item Type: Article
Status: Published
Creators/Authors:
CreatorsEmailPitt UsernameORCID
Pollett, JB
Corsi, KA
Weiss, KRkrw13@pitt.eduKRW13
Cooper, GMgmc8@pitt.eduGMC8
Barry, DA
Gharaibeh, Bburhan@pitt.eduBURHAN0000-0002-5947-1232
Huard, J
Centers: Other Centers, Institutes, or Units > Stem Cell Research Center
Date: 1 September 2007
Date Type: Publication
Journal or Publication Title: Stem Cells
Volume: 25
Number: 9
Page Range: 2302 - 2311
DOI or Unique Handle: 10.1634/stemcells.2006-0773
Schools and Programs: School of Medicine > Biochemistry and Molecular Genetics
School of Medicine > Orthopaedic Surgery
Swanson School of Engineering > Bioengineering
Refereed: Yes
ISSN: 1066-5099
MeSH Headings: Adult Stem Cells--cytology; Animals; Bone Morphogenetic Protein 4; Bone Morphogenetic Proteins--genetics; Bone Morphogenetic Proteins--pharmacology; Carrier Proteins--genetics; Cell Differentiation--genetics; Cell Lineage; Cell Transformation, Neoplastic--genetics; Cell Transformation, Neoplastic--pathology; Cells, Cultured; Gene Expression Regulation, Neoplastic; Mice; Mice, Inbred C57BL; Mice, SCID; Multipotent Stem Cells--cytology; Multipotent Stem Cells--pathology; Muscle Development--drug effects; Muscle Development--genetics; Muscle, Skeletal--cytology; MyoD Protein--genetics; MyoD Protein--physiology; Signal Transduction--genetics; Signal Transduction--physiology
PubMed ID: 17569791
Date Deposited: 09 Jun 2014 14:36
Last Modified: 29 Jan 2019 15:55
URI: http://d-scholarship.pitt.edu/id/eprint/21665

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