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Patient Derived Cell Culture and Isolation of CD133+ Putative Cancer Stem Cells from Melanoma
Published on: March 13, 2013
CD133+, CD166+CD44+, and CD24+CD44+ phenotypes fail to reliably identify cell populations with cancer stem cell
Manuele Giuseppe Muraro1, Valentina Mele, Silvio Däster
1Institute of Surgical Research and Hospital Management, Basel, Switzerland. giezzi@uhbs.ch
Abstract:
Increasing evidence that cancers originate from small populations of so-called cancer stem cells (CSCs), capable of surviving conventional chemotherapies and regenerating the original tumor, urges the development of novel CSC-targeted treatments. Screening of new anticancer compounds is conventionally conducted on established tumor cell lines, providing sufficient material for high-throughput studies. Whether tumor cell lines might comprise CSC populations resembling those of primary tumors, however, remains highly debated. We have analyzed the expression of defined phenotypic profiles, including CD133+, CD166+CD44+, and CD24+CD44+, reported as CSC-specific in human primary colorectal cancer (CRC), on a panel of 10 established CRC cell lines and evaluated their correlation with CSC properties. None of the putative CSC phenotypes consistently correlated with stem cell-like features, including spheroid formation ability, clonogenicity, aldehyde dehydrogenase-1 activity, and side population phenotype. Importantly, CRC cells expressing putative CSC markers did not exhibit increased survival when treated with chemotherapeutic drugs in vitro or display higher tumorigenicity in vivo. Thus, the expression of CD133 or the coexpression of CD166/CD44 or CD24/CD44 did not appear to reliably identify CSC populations in established CRC cell lines. Our findings question the suitability of cell lines for the screening of CSC-specific therapies and underline the urgency of developing novel platforms for anticancer drug discovery.
Insights
Established colorectal cancer cell lines do not reliably identify cancer stem cells (CSCs). This challenges their use in screening new CSC-targeted therapies and highlights the need for novel drug discovery platforms.
Area of Science:
- Oncology
- Cancer Biology
- Drug Discovery
Background:
- Cancer stem cells (CSCs) are implicated in tumor recurrence and therapy resistance.
- Novel CSC-targeted treatments are urgently needed.
- Established cancer cell lines are commonly used for drug screening.
Purpose of the Study:
- To investigate if established colorectal cancer (CRC) cell lines contain cancer stem cell (CSC) populations.
- To evaluate the correlation between known CSC markers and CSC properties in CRC cell lines.
- To assess the suitability of CRC cell lines for screening CSC-specific therapies.
Main Methods:
- Analysis of CSC marker expression (CD133+, CD166+CD44+, CD24+CD44+) in 10 CRC cell lines.
- Assessment of stem cell-like features: spheroid formation, clonogenicity, aldehyde dehydrogenase-1 activity, side population phenotype.
- Evaluation of chemoresistance and in vivo tumorigenicity of marker-expressing cells.
Main Results:
- No consistent correlation was found between putative CSC phenotypes and stem cell-like features in CRC cell lines.
- CRC cells expressing CSC markers did not show increased survival after chemotherapy treatment in vitro.
- These cells also did not display higher tumorigenicity in vivo.
- CD133, CD166/CD44, or CD24/CD44 expression did not reliably identify CSCs in CRC cell lines.
Conclusions:
- Established CRC cell lines may not accurately represent CSC populations found in primary tumors.
- The reliability of using current CRC cell lines for screening CSC-specific therapies is questioned.
- Novel platforms are essential for effective anticancer drug discovery targeting cancer stem cells.
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