Flow Cytometric Analysis of CD133- and EpCAM-Positive Cells in the Peripheral Blood of Patients with Lung Cancer

Tomasz Skirecki,Jerzy Kawiak,Grażyna Hoser,Dariusz Dziedzic,Joanna Domagała-Kulawik

doi:10.1007/s00005-013-0250-1

Abstract

Lung tumors are characterized by their high metastatic potential, which is the main cause of therapeutic failure. However, the exact cellular origin of metastasis remains unknown. Since the introduction of the cancer stem cell theory, lung cancer stem cells (LCSCs) have been thought to represent metastasis-founding cells. The current study aimed to evaluate whether LCSCs could be found in the circulation. Expression of the stem cell markers CD133 and EpCAM was confirmed in tumor and normal lung tissue by flow cytometry. Then, this technique was further used to investigate the expression of CD133 and EpCAM in the peripheral blood of 41 patients with primary lung cancer. Putative LCSCs (CD133+EpCAM+) were present in 6/7 tumor samples, and CD133+EpCAM+ cells were identified in the blood samples of 15 patients at a median level of 40/ml of blood. EpCAM+ cells were detected in 60 % of the patients, and the number of these cells was higher in patients with adenocarcinoma than patients with squamous cell carcinoma and was also higher in patients with less advanced disease. Moreover, the frequency of this subpopulation significantly correlated with the circulating level of SSEA-4+ cells. Additionally, CD133+EpCAM− cells were found in 87 % of the patients, and the numbers of these cells were significantly higher in patients with distant metastases and correlated with disease stage. This study confirmed the presence of an LCSC subpopulation with a CD133+EpCAM+ phenotype in the tumors and blood of patients with lung cancer, and these results suggest an important role for CD133 and EpCAM in lung cancer progression and their potential application as novel biomarkers of the disease.

Highlights

Lung cancer is an aggressive, malignant neoplasm with approximately 1.3 million new cases worldwide each year, and poor prognoses lead to high levels of mortality among men and women
This study confirmed the presence of an lung cancer stem cells (LCSCs) subpopulation with a CD133?EpCAM? phenotype in the tumors and blood of patients with lung cancer, and these results suggest an important role for CD133 and EpCAM in lung cancer progression and their potential application as novel biomarkers of the disease
We found that the fraction of CD133-EpCAM? cells varied between the histopathological types of non-small cell lung cancer evaluated, and this fraction was increased in the blood of patients with adenocarcinoma as compared to squamous cell carcinoma (0.0130 vs. 0.0027 %, p = 0.2; Fig. 3)

Summary

Introduction

Lung cancer is an aggressive, malignant neoplasm with approximately 1.3 million new cases worldwide each year, and poor prognoses lead to high levels of mortality among men and women. Two main histological types of lung cancer can be identified: non-small cell lung carcinoma (NSCLC) and small cell lung carcinoma (SCLC), which is highly aggressive and responsive to chemotherapy. Adenocarcinoma, an NSCLC subtype, was recently shown to be the most frequently observed type of lung cancer and is a candidate for targeted therapy (Alberg et al 2007). The low 5-year survival rate for patients with lung cancer is related to the occurrence of early, widespread metastases (including those to the bone marrow, bones, brain, liver, and pleural cavity) and a high rate of relapse, regardless of whether initial treatment led to remission (Krzakowski 2010).

Methods

Results

Conclusion