Abstract
Cancer stem cells (CSCs) are defined as a small population of cancer cells with the properties of high self-renewal, differentiation, and tumor-initiating functions. Recent studies have demonstrated that aldehyde dehydrogenase 1 (ALDH1) is a marker for CSCs in adult cancers. Although CSCs have been identified in some different types of pediatric solid tumors, there have been no studies regarding the efficacy of ALDH1 as a marker for CSCs. Therefore, in order to elucidate whether ALDH1 can be used as a marker for CSCs of pediatric sarcoma, we examined the characteristics of a population of cells with a high ALDH1 activity (ALDH1high cells) in rhabdomyosarcoma (RMS), the most common soft tissue sarcoma in children. We used the human embryonal RMS (eRMS) cell lines RD and KYM-1, and sorted the cells into two subpopulations of ALDH1high cells and cells with a low ALDH1 activity (ALDH1low cells). Consequently, we found that the ALDH1high cells comprised 3.9% and 8.2% of the total cell population, respectively, and showed a higher capacity for self-renewal and tumor formation than the ALDH1low cells. With regard to chemoresistance, the survival rate of the ALDH1high cells was found to be higher than that of the ALDH1low cells following treatment with chemotherapeutic agents for RMS. Furthermore, the ALDH1high cells exhibited a higher degree of pluripotency and gene expression of Sox2, which is one of the stem cell markers. Taken together, the ALDH1high cells possessed characteristics of CSCs, including colony formation, chemoresistance, differentiation and tumor initiation abilities. These results suggest that ALDH1 is a potentially useful marker of CSCs in eRMS.
Highlights
Cancer stem-like cells (CSCs) are defined as a small population of cancer cells with the properties of high tumor-initiating, self-renewal and differentiation functions [1]
In the RD cells, the ratio of the ALDH1high cells stained with BAAA was 4.1%, while that of those stained with BAAA and DEAB as a negative control was 0.2%
CSCs have been identified in various malignancies, including acute myeloid leukemia [15], brain tumors [16], hepatocellular carcinoma [17], breast cancer [7], lung cancer [18], pancreatic cancer [19] and ovarian cancer [8]
Summary
Cancer stem-like cells (CSCs) are defined as a small population of cancer cells with the properties of high tumor-initiating, self-renewal and differentiation functions [1]. CSCs are resistant to standard therapies, such as chemotherapy and radiotherapy, and responsible for tumor relapse after treatment as well as invasion and metastasis [2, 3]. Despite significant improvements in survival over the past few decades, more than one-third of RMS patients continue to die of the disease [4]. Patients with metastatic or refractory tumors exhibit a severe prognosis [5]. Augmenting conventional regimens has not significantly improved survival, and research for CSCs of RMS is very important for improving the prognosis, as these cells are supposed to induce relapse and metastasis. CD133 (prominin-1) has been reported to be a marker for CSCs [6], it exists on normal stem cells, and it is necessary to identify other markers for RMS
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