Aldehyde Dehydrogenase 1, a Potential Marker for Cancer Stem Cells in Human Sarcoma

Abstract

Tumors contain a small population of cancer stem cells (CSC) proposed to be responsible for tumor maintenance and relapse. Aldehyde dehydrogenase 1 (ALDH1) activity has been used as a functional stem cell marker to isolate CSCs in different cancer types. This study used the Aldefluor® assay and fluorescence-activated cell sorting (FACS) analysis to isolate ALDH1high cells from five human sarcoma cell lines and one primary chordoma cell line. ALDH1high cells range from 0.3% (MUG-Chor1) to 4.1% (SW-1353) of gated cells. Immunohistochemical staining, analysis of the clone formation efficiency, and xCELLigence microelectronic sensor technology revealed that ALDH1high cells from all sarcoma cell lines have an increased proliferation rate compared to ALDH1low cells. By investigating of important regulators of stem cell biology, real-time RT-PCR data showed an increased expression of c-Myc, β-catenin, and SOX-2 in the ALDH1high population and a significant higher level of ABCG2. Statistical analysis of data demonstrated that ALDH1high cells of SW-982 and SW-1353 showed higher resistance to commonly used chemotherapeutic agents like doxorubicin, epirubicin, and cisplatin than ALDH1low cells. This study demonstrates that in different sarcoma cell lines, high ALDH1 activity can be used to identify a subpopulation of cells characterized by a significantly higher proliferation rate, increased colony forming, increased expression of ABC transporter genes and stemness markers compared to control cells. In addition, enhanced drug resistance was demonstrated.

The molecular aspects of chordoma

“…Furthermore, coupling the chemotherapeutic agents etoposide and cisplatin with the differentiation agent retinoic acid increased the inhibition of cell growth in U-CH1 cells, suggesting that the chemoresistance of chordomas may be a result of the presence of cancer stem cells [8]. ALDH, a common marker for cancer stem cells, was observed in a very small portion of the MUG-Chor cell line population [52].…”

CD26 a cancer stem cell marker and therapeutic target

“…Furthermore, in solid tumors, it is possible to identify the side population (SP), characterized by the expulsion of Hoestch33342 1 dye within CSCs due to the presence of efflux pumps in these cells [12]. Aldehyde dehydrogenase 1 (ALDH1) activity has also been used as a functional stem cell marker to isolate CSCs [13].…”

Twist1 is essential in maintaining mesenchymal state and tumor-initiating properties in synovial sarcoma

“…From that point of view, MSCs can be considered as candidate TICs of SS [9]. Regarding stem cell-like cancer cell populations in SS, Terry and Nielsen reported that CD133 may mark TIC in SS [10], and Lohberger et al reported aldehyde dehydrogenase (ALDH) could be a potential marker for SS [11]. In addition, Wu et al examined three cases of primary SSs and identified a side-population (SP) group harboring properties similar to those of TICs in a synovial sarcoma [12].…”