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

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 CD49fhi/CD90lo cell phenotype produced an aggressive tumor. Multiple lines of evidence demonstrated that inhibiting CD49f decreased the tumor-forming ability. Furthermore, the CD49fhi/CD90lo 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.

Extracellular vesicles from bone marrow mesenchymal stem/stromal cells transport tumor regulatory microRNA, proteins, and metabolites

“…As a proof of concept we have confirmed expression of 7 proteins; two proteins confirm the origin of the hMSCs EVs (CD90 and CD81) [37] and five known proteins associated with tumor proliferation and anti-metastasis [38-42]. Proteomics data supports the notion that the protein sorting in the EVs is not a random event: a) the constancy between the proteomic assays on EVs preparations from two different donors.…”

Role of Cancer Stem Cells in Cholangiocarcinoma and Therapeutic Implications

“…CD49f, which is also known as integrin α6, is found in adult stem cells [90]. Furthermore, CD49f plays an important role in the generation of some solid tumors, including osteosarcoma and hemangioma [91,92]. In CCA, Ding et al [62] reported that iCCA tissues exhibited higher expression of CD49f than non-tumor samples.…”

Pediatric sarcomas (Review)

“…However, no further study has been published to support the utility of CD117 in osteosarcoma. Previously, two independent groups have reported that CD49f may serve in osteosarcoma as another marker that can distinguish CSCs from the cells with limited tumorigenic capacity ( 14 ). Nevertheless, these two studies brought contradictory results.…”