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Published on: October 30, 2011
Establishment of a tumor sphere cell line from a metastatic brain neuroendocrine tumor
Ryoichi Iwata1, Masato Maruyama2, Tomoki Ito3
1Department of Neurosurgery, Kansai Medical University, Hirakata, Japan.
Abstract:
Neuroendocrine tumors are rare, and little is known about the existence of cancer stem cells in this disease. Identification of the tumorigenic population will contribute to the development of effective therapies targeting neuroendocrine tumors. Surgically resected brain metastases from a primary neuroendocrine tumor of unknown origin were dissociated and cultured in serum-free neurosphere medium. Stem cell properties, including self-renewal, differentiation potential, and stem cell marker expression, were examined. Tumor formation was evaluated using intracranial xenograft models. The effect of temozolomide was measured in vitro by cell viability assays. We established the neuroendocrine tumor sphere cell line ANI-27S, which displayed stable exponential growth, virtually unlimited expansion in vitro, and expression of stem-cell markers such as CD133, nestin, Sox2, and aldehyde dehydrogenase. FBS-induced differentiation decreased Sox2 and nestin expression. On the basis of real-time PCR, ANI-27S cells expressed the neuroendocrine markers synaptophysin and chromogranin A. Intracranial xenotransplanted brain tumors recapitulated the original patient tumor and temozolomide exhibited cytotoxic effects on tumor sphere cells. For the first time, we demonstrated the presence of a sphere-forming, stem cell-like population in brain metastases from a primary neuroendocrine tumor. We also demonstrated the potential therapeutic effects of temozolomide for this disease.
Insights
Researchers identified cancer stem cells in brain metastases of neuroendocrine tumors. These cells, termed ANI-27S, show self-renewal and express stem cell markers, offering new therapeutic targets for this rare cancer.
Area of Science:
- Oncology
- Neuroscience
- Stem Cell Biology
Background:
- Neuroendocrine tumors (NETs) are rare, with limited understanding of their cancer stem cell (CSC) populations.
- Identifying CSCs is crucial for developing targeted therapies for NETs.
Purpose of the Study:
- To identify and characterize cancer stem cells in brain metastases of neuroendocrine tumors.
- To evaluate the therapeutic potential of temozolomide against these identified cells.
Main Methods:
- Establishing a neuroendocrine tumor sphere cell line (ANI-27S) from brain metastases.
- Assessing stem cell properties: self-renewal, differentiation, and marker expression (CD133, nestin, Sox2, aldehyde dehydrogenase).
- Evaluating tumor formation in intracranial xenograft models and temozolomide's efficacy via in vitro viability assays.
Main Results:
- The ANI-27S cell line exhibited characteristics of cancer stem cells, including self-renewal, marker expression, and neuroendocrine marker expression (synaptophysin, chromogranin A).
- Differentiation induction led to decreased expression of Sox2 and nestin.
- Xenograft models showed that ANI-27S cells recapitulated the original tumor, and temozolomide demonstrated cytotoxic effects.
Conclusions:
- This study provides the first evidence of a sphere-forming, stem cell-like population in neuroendocrine tumor brain metastases.
- The findings suggest that temozolomide may have potential therapeutic effects against these neuroendocrine tumor stem cells.
