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Updated: Jun 3, 2026
Obtaining Cancer Stem Cell Spheres from Gynecological and Breast Cancer Tumors
Published on: March 1, 2020
High CD133 expression levels in gastrointestinal stromal tumors
Fabio Bozzi1, Elena Conca, Giacomo Manenti
1Laboratory of Experimental Molecular Pathology, Department of Pathology, Fondazione IRCCS, Istituto Nazionale Tumori, Milan, Italy.
Background:
Gastrointestinal stromal tumours (GISTs) have activating KIT or PDGFRA gene mutations. Imatinib mesylate, which targets KIT and PDGFRA, is effective in treating GISTs, but 90% of GIST patients become imatinib-resistant as a result of acquiring secondary KIT mutations. Recent findings suggest that tumour growth can be driven by mutated self-renewing progenitors known as cancer stem cells (CSCs), which are believed to be present in all neoplastic proliferations and are thought to accumulate mutations. It is therefore possible that the acquisition of secondary KIT mutations during imatinib treatment may occur in putative GIST CSCs.
Methods:
Using flow cytometry, in vivo murine xenografts and molecular characterization, we tried to identify putative GIST CSCs by looking for the occurrence of common CSC markers such as KIT, CD133, CD90, CD44, and CD34 in 18 surgical samples obtained from nine untreated and nine imatinib-treated KIT-mutated GIST patients.
Results:
The results indicated the homogeneous and previously unreported expression of CD133 (18/18), CD90 (15/16), and CD44 (12/14), together with KIT (18/18) and CD34 (13/18). This profile is similar to that identified in bone marrow mesenchymal progenitors and does not seem to be significantly modified by imatinib as only marginal changes in KIT and CD133 expression (P ≤ 0.05, Mann-Whitney test) were found in the treated samples.
Conclusions:
These findings suggest that GISTs are a clonal expansion of quite primitive cells that strictly depend on KIT oncogenic addiction, and have no cancer/stem cell component that can be detected by means of the antigens used in this study.
Insights
Gastrointestinal stromal tumors (GISTs) show primitive cell markers, not cancer stem cells, even after imatinib treatment. These GISTs are a clonal expansion dependent on KIT mutations.
Area of Science:
- Oncology
- Gastroenterology
- Molecular Biology
Background:
- Gastrointestinal stromal tumors (GISTs) are driven by KIT or PDGFRA mutations.
- Imatinib resistance develops in 90% of GIST patients due to secondary KIT mutations.
- Cancer stem cells (CSCs) are implicated in tumor growth and mutation accumulation.
Purpose of the Study:
- To identify putative GIST cancer stem cells (CSCs).
- To investigate the role of CSCs in imatinib resistance in GISTs.
Main Methods:
- Flow cytometry and molecular characterization of GIST samples.
- Analysis of CSC markers (KIT, CD133, CD90, CD44, CD34) in untreated and imatinib-treated GIST patients.
- In vivo murine xenografts were utilized.
Main Results:
- GISTs uniformly express CD133, CD90, CD44, KIT, and CD34.
- This marker profile resembles bone marrow mesenchymal progenitors.
- Imatinib treatment caused only minor changes in KIT and CD133 expression.
Conclusions:
- GISTs represent a clonal expansion of primitive cells.
- These cells exhibit strict dependence on KIT oncogenic signaling.
- No detectable cancer/stem cell component was found using the studied antigens.
