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CD133 expression in chemo-resistant Ewing sarcoma cells.

Xiaohua Jiang¹, Ynnez Gwye, Darren Russell

¹Saban Research Institute, Childrens Hospital Los Angeles, 4650 Sunset Blvd, Los Angeles, CA 90027, USA.

|March 30, 2010

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High CD133 expression in Ewing sarcoma family tumors (ESFT) is linked to drug resistance in some cases. However, this association is heterogeneous, requiring further investigation into its role in therapeutic resistance.

Area of Science:

Oncology
Cancer Stem Cell Biology
Molecular Oncology

Background:

Cancer stem cells (CSCs) drive tumor initiation and therapy resistance in various human cancers.
Ewing sarcoma family tumors (ESFT) are aggressive, with drug resistance and recurrence posing significant clinical challenges.
CD133, a cell surface protein, has been identified as a potential marker for tumor-initiating cells in ESFT.

Purpose of the Study:

To investigate the association between high CD133 expression and drug resistance in ESFT.
To evaluate CD133 (PROM1 gene) and CD133 protein expression in ESFT tumors and cell lines.
To compare the tumorigenicity and chemosensitivity of CD133-positive and CD133-negative cell populations.

Main Methods:

RT-PCR was used to determine PROM1 gene expression in ESFT samples.

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Western blot, FACS, and immunostaining assessed CD133 protein levels.

FACS-sorted CD133+ and CD133- cell fractions were analyzed for proliferation, colony formation, tumorigenicity, and chemosensitivity via MTS assays.

Main Results:

PROM1 expression was low in most ESFT tumors, but highly over-expressed in 4 out of 48 cases.
Two patients with PROM1-overexpressing tumors showed primary drug resistance and rapid progression.
While most cell lines showed no difference in chemoresistance between CD133+ and CD133- fractions, one line exhibited a hierarchy where CD133+ cells were more resistant.

Conclusions:

Up to 10% of ESFT cases exhibit high PROM1 expression.
The CD133+ fraction demonstrated increased drug resistance in some ESFT tumors and cell lines, but not all.
Heterogeneity in PROM1/CD133 expression exists in ESFT, with high PROM1 correlating with chemo-resistance in specific instances, warranting further prospective studies.