Asset Details
Do you wish to reserve the book?
Generation of Osteosarcomas from a Combination of Rb Silencing and c‐Myc Overexpression in Human Mesenchymal Stem Cells
Hey, we have placed the reservation for you!
By the way, why not check out events that you can attend while you pick your title.
Oops! Something went wrong.
Looks like we were not able to place the reservation. Kindly try again later.
Are you sure you want to remove the book from the shelf?
Generation of Osteosarcomas from a Combination of Rb Silencing and c‐Myc Overexpression in Human Mesenchymal Stem Cells
Do you wish to request the book?
Generation of Osteosarcomas from a Combination of Rb Silencing and c‐Myc Overexpression in Human Mesenchymal Stem Cells
Please be aware that the book you have requested cannot be checked out. If you would like to checkout this book, you can reserve another copy
We have requested the book for you!
Your request is successful and it will be processed during the Library working hours. Please check the status of your request in My Requests.
Oops! Something went wrong.
Looks like we were not able to place your request. Kindly try again later.
Journal Article
Generation of Osteosarcomas from a Combination of Rb Silencing and c‐Myc Overexpression in Human Mesenchymal Stem Cells
2017
Overview
Osteosarcoma (OS) was a malignant tumor occurring with unknown etiology that made prevention and early diagnosis difficult. Mesenchymal stem cells (MSCs), which were found in bone marrow, were claimed to be a possible origin of OS but with little direct evidence. We aimed to characterize OS cells transformed from human MSCs (hMSCs) and identify their association with human primary OS cells and patient survival. Genetic modification with p53 or retinoblastoma (Rb) knockdown and c‐Myc or Ras overexpression was applied for hMSC transformation. Transformed cells were assayed for proliferation, differentiation, tumorigenecity, and gene expression profile. Only the combination of Rb knockdown and c‐Myc overexpression successfully transformed hMSCs derived from four individual donors, with increasing cell proliferation, decreasing cell senescence rate, and increasing ability to form colonies and spheres in serum‐free medium. These transformed cells lost the expression of certain surface markers, increased in osteogenic potential, and decreased in adipogenic potential. After injection in immunodeficient mice, these cells formed OS‐like tumors, as evidenced by radiographic analyses and immunohistochemistry of various OS markers. Microarray with cluster analysis revealed that these transformed cells have gene profiles more similar to patient‐derived primary OS cells than their normal MSC counterparts. Most importantly, comparison of OS patient tumor samples revealed that a combination of Rb loss and c‐Myc overexpression correlated with a decrease in patient survival. This study successfully transformed human MSCs to OS‐like cells by Rb knockdown and c‐Myc overexpression that may be a useful platform for further investigation of preventive and target therapy for human OS. Stem Cells Translational Medicine 2017;6:512–526
Publisher
Oxford University Press,John Wiley and Sons Inc
Subject
/ Animals
/ Cancer
/ Cell Transformation, Neoplastic - genetics
/ Cell Transformation, Neoplastic - metabolism
/ Cell Transformation, Neoplastic - pathology
/ c‐Myc
/ DNA
/ Enabling Technologies for Cell‐Based Clinical Translation
/ Etiology
/ Gene Expression Regulation, Neoplastic
/ Genes
/ Humans
/ Mesenchymal Stem Cell Transplantation
/ Mesenchymal Stem Cells - metabolism
/ Mesenchymal Stem Cells - pathology
/ Mutation
/ Patients
/ Proto-Oncogene Proteins c-myc - genetics
/ Proto-Oncogene Proteins c-myc - metabolism
/ Retina
/ Retinoblastoma (Rb) knockdown
/ Retinoblastoma Protein - deficiency
/ Retinoblastoma Protein - genetics
/ Sarcoma
/ Studies
/ Tumors
