Genetically transforming human osteoblasts to sarcoma: Development of an osteosarcoma model

Yi Yang, Rui Yang, Michael Roth, Sajida Piperdi, Wendong Zhang, Howard Dorfman, Pulivarthi Rao, Amy Park, Sandeep Tripathi, Carrie Freeman, Yunjia Zhang, Rebecca Sowers, Jeremy Rosenblum, David S. Geller, Bang H. Hoang, Jonathan Gill, Richard Gorlick

Research output: Contribution to journalArticle

10 Citations (Scopus)

Abstract

Osteosarcoma is the most common primary malignant bone tumor in children and young adults. Although histologically defined by the presence of malignant osteoid, the tumor possesses lineage multipotency suggesting it could be derived from a cell anywhere on the differentiation pathway between a mesenchymal stem cell (MSC) and a mature osteoblast. To determine if preosteoblasts (pOB) could be the cell of origin differentiated MSCs were transformed with defined genetic elements. MSCs and pOB differentiated from the same MSCs were serially transformed with the oncogenes hTERT, SV40 large T antigen and H-Ras. Assays were performed to determine their tumorigenic properties, differentiation capacity and histologic appearance. When subcutaneously implanted in immunocompromised mice, cell lines derived from transformed MSC and pOB formed tumors in 4 weeks. In contrast to the transformed MSC, the pOB tumors demonstrated a histological appearance characteristic of osteosarcoma. The cell lines derived from the transformed pOB only had osteogenic and chondrogenic differentiation potential, but not adipogenic ones. However, the transformed MSC cells and standard osteosarcoma cell lines maintained their tri-lineage differentiation capacity. The inability of the transformed pOB cell line to undergo adipogenic differentiation, may suggest that osteosarcoma is derived from a cell intermediate in differentiation between an MSC and a pOB, with partial commitment to the osteoblastic lineage.

Original languageEnglish (US)
Pages (from-to)484-494
Number of pages11
JournalGenes and Cancer
Volume8
Issue number1-2
DOIs
StatePublished - Jan 1 2017

Fingerprint

Osteosarcoma
Osteoblasts
Mesenchymal Stromal Cells
Sarcoma
Transformed Cell Line
Neoplasms
Polyomavirus Transforming Antigens
Viral Tumor Antigens
Oncogenes
Young Adult
Bone and Bones
Cell Line

Keywords

  • Mesenchymal stem cells
  • Osteoblast
  • Osteosarcoma

ASJC Scopus subject areas

  • Genetics
  • Cancer Research

Cite this

Genetically transforming human osteoblasts to sarcoma : Development of an osteosarcoma model. / Yang, Yi; Yang, Rui; Roth, Michael; Piperdi, Sajida; Zhang, Wendong; Dorfman, Howard; Rao, Pulivarthi; Park, Amy; Tripathi, Sandeep; Freeman, Carrie; Zhang, Yunjia; Sowers, Rebecca; Rosenblum, Jeremy; Geller, David S.; Hoang, Bang H.; Gill, Jonathan; Gorlick, Richard.

In: Genes and Cancer, Vol. 8, No. 1-2, 01.01.2017, p. 484-494.

Research output: Contribution to journalArticle

Yang, Y, Yang, R, Roth, M, Piperdi, S, Zhang, W, Dorfman, H, Rao, P, Park, A, Tripathi, S, Freeman, C, Zhang, Y, Sowers, R, Rosenblum, J, Geller, DS, Hoang, BH, Gill, J & Gorlick, R 2017, 'Genetically transforming human osteoblasts to sarcoma: Development of an osteosarcoma model', Genes and Cancer, vol. 8, no. 1-2, pp. 484-494. https://doi.org/10.18632/genesandcancer.133
Yang, Yi ; Yang, Rui ; Roth, Michael ; Piperdi, Sajida ; Zhang, Wendong ; Dorfman, Howard ; Rao, Pulivarthi ; Park, Amy ; Tripathi, Sandeep ; Freeman, Carrie ; Zhang, Yunjia ; Sowers, Rebecca ; Rosenblum, Jeremy ; Geller, David S. ; Hoang, Bang H. ; Gill, Jonathan ; Gorlick, Richard. / Genetically transforming human osteoblasts to sarcoma : Development of an osteosarcoma model. In: Genes and Cancer. 2017 ; Vol. 8, No. 1-2. pp. 484-494.
@article{a05a01e84c8044638d4f864e88da2aee,
title = "Genetically transforming human osteoblasts to sarcoma: Development of an osteosarcoma model",
abstract = "Osteosarcoma is the most common primary malignant bone tumor in children and young adults. Although histologically defined by the presence of malignant osteoid, the tumor possesses lineage multipotency suggesting it could be derived from a cell anywhere on the differentiation pathway between a mesenchymal stem cell (MSC) and a mature osteoblast. To determine if preosteoblasts (pOB) could be the cell of origin differentiated MSCs were transformed with defined genetic elements. MSCs and pOB differentiated from the same MSCs were serially transformed with the oncogenes hTERT, SV40 large T antigen and H-Ras. Assays were performed to determine their tumorigenic properties, differentiation capacity and histologic appearance. When subcutaneously implanted in immunocompromised mice, cell lines derived from transformed MSC and pOB formed tumors in 4 weeks. In contrast to the transformed MSC, the pOB tumors demonstrated a histological appearance characteristic of osteosarcoma. The cell lines derived from the transformed pOB only had osteogenic and chondrogenic differentiation potential, but not adipogenic ones. However, the transformed MSC cells and standard osteosarcoma cell lines maintained their tri-lineage differentiation capacity. The inability of the transformed pOB cell line to undergo adipogenic differentiation, may suggest that osteosarcoma is derived from a cell intermediate in differentiation between an MSC and a pOB, with partial commitment to the osteoblastic lineage.",
keywords = "Mesenchymal stem cells, Osteoblast, Osteosarcoma",
author = "Yi Yang and Rui Yang and Michael Roth and Sajida Piperdi and Wendong Zhang and Howard Dorfman and Pulivarthi Rao and Amy Park and Sandeep Tripathi and Carrie Freeman and Yunjia Zhang and Rebecca Sowers and Jeremy Rosenblum and Geller, {David S.} and Hoang, {Bang H.} and Jonathan Gill and Richard Gorlick",
year = "2017",
month = "1",
day = "1",
doi = "10.18632/genesandcancer.133",
language = "English (US)",
volume = "8",
pages = "484--494",
journal = "Genes and Cancer",
issn = "1947-6019",
publisher = "SAGE Publications Inc.",
number = "1-2",

}

TY - JOUR

T1 - Genetically transforming human osteoblasts to sarcoma

T2 - Development of an osteosarcoma model

AU - Yang, Yi

AU - Yang, Rui

AU - Roth, Michael

AU - Piperdi, Sajida

AU - Zhang, Wendong

AU - Dorfman, Howard

AU - Rao, Pulivarthi

AU - Park, Amy

AU - Tripathi, Sandeep

AU - Freeman, Carrie

AU - Zhang, Yunjia

AU - Sowers, Rebecca

AU - Rosenblum, Jeremy

AU - Geller, David S.

AU - Hoang, Bang H.

AU - Gill, Jonathan

AU - Gorlick, Richard

PY - 2017/1/1

Y1 - 2017/1/1

N2 - Osteosarcoma is the most common primary malignant bone tumor in children and young adults. Although histologically defined by the presence of malignant osteoid, the tumor possesses lineage multipotency suggesting it could be derived from a cell anywhere on the differentiation pathway between a mesenchymal stem cell (MSC) and a mature osteoblast. To determine if preosteoblasts (pOB) could be the cell of origin differentiated MSCs were transformed with defined genetic elements. MSCs and pOB differentiated from the same MSCs were serially transformed with the oncogenes hTERT, SV40 large T antigen and H-Ras. Assays were performed to determine their tumorigenic properties, differentiation capacity and histologic appearance. When subcutaneously implanted in immunocompromised mice, cell lines derived from transformed MSC and pOB formed tumors in 4 weeks. In contrast to the transformed MSC, the pOB tumors demonstrated a histological appearance characteristic of osteosarcoma. The cell lines derived from the transformed pOB only had osteogenic and chondrogenic differentiation potential, but not adipogenic ones. However, the transformed MSC cells and standard osteosarcoma cell lines maintained their tri-lineage differentiation capacity. The inability of the transformed pOB cell line to undergo adipogenic differentiation, may suggest that osteosarcoma is derived from a cell intermediate in differentiation between an MSC and a pOB, with partial commitment to the osteoblastic lineage.

AB - Osteosarcoma is the most common primary malignant bone tumor in children and young adults. Although histologically defined by the presence of malignant osteoid, the tumor possesses lineage multipotency suggesting it could be derived from a cell anywhere on the differentiation pathway between a mesenchymal stem cell (MSC) and a mature osteoblast. To determine if preosteoblasts (pOB) could be the cell of origin differentiated MSCs were transformed with defined genetic elements. MSCs and pOB differentiated from the same MSCs were serially transformed with the oncogenes hTERT, SV40 large T antigen and H-Ras. Assays were performed to determine their tumorigenic properties, differentiation capacity and histologic appearance. When subcutaneously implanted in immunocompromised mice, cell lines derived from transformed MSC and pOB formed tumors in 4 weeks. In contrast to the transformed MSC, the pOB tumors demonstrated a histological appearance characteristic of osteosarcoma. The cell lines derived from the transformed pOB only had osteogenic and chondrogenic differentiation potential, but not adipogenic ones. However, the transformed MSC cells and standard osteosarcoma cell lines maintained their tri-lineage differentiation capacity. The inability of the transformed pOB cell line to undergo adipogenic differentiation, may suggest that osteosarcoma is derived from a cell intermediate in differentiation between an MSC and a pOB, with partial commitment to the osteoblastic lineage.

KW - Mesenchymal stem cells

KW - Osteoblast

KW - Osteosarcoma

UR - http://www.scopus.com/inward/record.url?scp=85031755163&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=85031755163&partnerID=8YFLogxK

U2 - 10.18632/genesandcancer.133

DO - 10.18632/genesandcancer.133

M3 - Article

AN - SCOPUS:85031755163

VL - 8

SP - 484

EP - 494

JO - Genes and Cancer

JF - Genes and Cancer

SN - 1947-6019

IS - 1-2

ER -