High CD49f expression is associated with osteosarcoma tumor progression: a study using patient‐derived primary cell cultures

Cancer Medicine

Patrice Penfornis²  David Z. Cai³  Michael R. Harris³  Ryan Walker³  David Licini¹  Joseph D. A. Fernandes²  Griffin Orr²  Tejaswi Koganti²  Chindo Hicks²  Spandana Induru³  Mark S. Meyer¹  Rama Khokha⁴  Jennifer Barr⁵ 

[1] Department of Orthopedics, Oschner Medical Center, New Orleans, Louisiana;Cancer Institute, University of Mississippi Medical Center, Jackson, Mississippi;Center for Stem Cell Research and Regenerative Medicine, Tulane University, New Orleans, Louisiana;Ontario Cancer Institute, Toronto, canada;Department of Orthopedic Surgery, University of Mississippi Medical Center, Jackson, Mississippi

关键词: Cancer stem cell;    CD49f;    integrin;    osteosarcoma;    tumor‐initiating cell;    tumor progression;   

DOI  :  10.1002/cam4.249

来源: Wiley

【 摘 要 】

Abstract

Overall prognosis for osteosarcoma (OS) is poor despite aggressive treatment options. Limited access to primary tumors, technical challenges in processing OS tissues, and the lack of well-characterized primary cell cultures has hindered our ability to fully understand the properties of OS tumor initiation and progression. In this study, we have isolated and characterized cell cultures derived from four central high-grade human OS samples. Furthermore, we used the cell cultures to study the role of CD49f in OS progression. Recent studies have implicated CD49f in stemness and multipotency of both cancer stem cells and mesenchymal stem cells. Therefore, we investigated the role of CD49f in osteosarcomagenesis. First, single cell suspensions of tumor biopsies were subcultured and characterized for cell surface marker expression. Next, we characterized the growth and differentiation properties, sensitivity to chemotherapy drugs, and anchorage-independent growth. Xenograft assays showed that cell populations expressing CD49f^hi/CD90^lo cell phenotype produced an aggressive tumor. Multiple lines of evidence demonstrated that inhibiting CD49f decreased the tumor-forming ability. Furthermore, the CD49f^hi/CD90^lo cell population is generating more aggressive OS tumor growth and indicating this cell surface marker could be a potential candidate for the isolation of an aggressive cell type in OSs.

【 授权许可】

CC BY   
© 2014 The Authors. Cancer Medicine published by John Wiley & Sons Ltd.

Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.