Clinical Significance of Cancer Stem Cell Markers CD133 and CXCR4 in Osteosarcomas.

Azam Mardani,Seyed Hamzeh Mousavie,Tina Shooshtarizadeh,Zahra Madjd Jabari,Elmira Gheytanchi

doi:10.31557/apjcp.2020.21.1.67

Abstract

Objective:Osteosarcomas (OS) is one the most common primary bone malignancy in humans with the lungs metastasis in most cases. Metastasis and recurrence of OS is attributed to cancer stem cells (CSCs). Our study aimed to evaluate the clinical significance of CD133 and C-X-C chemokine receptor type 4 (CXCR4) as the frequently applied markers for CSCs in OS patients. Methods:In this cross-sectional, a total of 50 tissue samples from the patients with primary OS were immunohistochemically examined to detect the expression of CD133 and CXCR4. The associations of the relative expression and clinical significance of each marker were also evaluated. Results:High level expression of CD133 was detected in 26% of OS patient tissues. Of the 12 patients who showed lung metastasis, 5 cases showed high expression of CD133 with marginal trend correlation (P=0.06). No significant correlation was observed between CD133 expression and clinicopathological factors. Only 36% of cases showed CXCR4 expression which was not significantly correlated with gender, age, tumor size, necrosis, stage and metastasis (P>0.05). Clinically, patients with concomitant CD133/CXCR4 expression had significant association with lung metastasis (P=0.05). Conclusion:Our findings showed that concomitant expression of CSC markers CD133/CXCR4 might had a synergistic effect on the OS poor prognosis. These markers could be considered as potential therapeutic candidates of OS targeted therapy.

Highlights

Bone cancers are a group of mesenchymal malignancies that include osteosarcoma (OS) and chondrosarcoma with clinical, histological, and molecular heterogeneity (Gibbs et al, 2005)
Many studies have been focused on Chemokines as the main recruiting factors and on chemokine receptors produced by metastatic niche which lead to tumor cell attraction and homing in distant sites (Lazennec et al, 2010; Balkwill et al, 2004; Kryczek et al, 2007)
He at al showed that mRNA of the stemness genes such as octamer-binding transcription factor4 (Oct-4) and NANOG, and the metastasis-related receptor CXCR4 were highly expressed in CD133+ OS cells (He et al, 2012)

Summary

Introduction

Bone cancers are a group of mesenchymal malignancies that include osteosarcoma (OS) and chondrosarcoma with clinical, histological, and molecular heterogeneity (Gibbs et al, 2005). OS, called osteogenic sarcoma, is the most common malignant primary bone tumor in humans which is exhibited with the lungs micro metastasis as the main causes of OS deaths at diagnosis in approximately 95% of the patients (Adhikari et al, 2010). The lung considered as the most common distant metastatic site for OS with a high-grade histopathology. Despite multidisciplinary therapeutic strategies including intensive or neoadjuvant chemotherapy specially for high-grade osteosarcoma after aggressive surgical resection (mostly limb-sparing) and radiotherapy, the survival rate of osteosarcoma patients is still low (Adhikari et al, 2010). In order to design appropriate therapeutic strategies and to overcome OS tumor progression, it is essential to understand the molecular mechanisms underlying chemo resistance and metastasis (Tobe et al, 2017)

Methods

Results

Conclusion