Establishment of a tumor sphere cell line from a metastatic brain neuroendocrine tumor

Ryoichi Iwata, Masato Maruyama, Tomoki Ito, Yosuke Nakano, Yonehiro Kanemura, Taro Koike, Souichi Oe, Kunikazu Yoshimura, Masahiro Nonaka, Shosaku Nomura, Tetsuo Sugimoto, Hisao Yamada, Akio Asai

Research output: Contribution to journalArticlepeer-review

3 Citations (Scopus)


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.

Original languageEnglish
Pages (from-to)211-219
Number of pages9
JournalMedical Molecular Morphology
Issue number4
Publication statusPublished - Dec 1 2017
Externally publishedYes


  • Aldefluor™
  • CD133
  • Cancer stem cells
  • Metastatic brain tumor
  • Neuroendocrine tumor
  • Temozolomide

ASJC Scopus subject areas

  • Pathology and Forensic Medicine
  • Molecular Biology


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