Modeling craniopharyngioma for drug screening reveals a neuronal mechanism for tumor growth
Tumors occurring along the hypothalamus-pituitary axis receive axonal projection from neuroendocrine neurons, but it remains unclear whether neuroendocrine neuronal activity drives tumor expansion. Craniopharyngioma is a common suprasellar tumor with a propensity for invading the hypothalamus, leading to devastating endocrine and metabolic disorders. Here, we developed two autochthonous animal models that faithfully recapitulate the molecular pathology, clinical manifestations, and transcriptomic profiles of papillary craniopharyngioma. Using high-throughput drug screening, we identified 74 compounds with potent antitumor efficacy. The administration of (<i>S</i>)-amlodipine besylate achieved tumor regression in vivo, potentially by abrogating calcium transients and neuron-to-tumor chemical transmission. Chemogenetic manipulation of neuroendocrine neuronal activity bidirectionally regulated tumor cell growth in our mouse model, suggesting that craniopharyngioma hijacks hypothalamic neurons to promote tumor progression. These findings deepen our understanding of suprasellar tumor biology and offer promising avenues for clinical exploration of effective chemotherapies.
Authors
- Zhifang Xing
- Xiangbing Qi (ORCID: https://orcid.org/0000-0002-7139-5164)
- Qingfeng Wu (ORCID: https://orcid.org/0000-0003-3272-6247)
- Yinqing Li (ORCID: https://orcid.org/0000-0002-9096-8482)
- Peng Cao (ORCID: https://orcid.org/0000-0001-7739-6857)
- Yanfei Jia (ORCID: https://orcid.org/0000-0003-0476-9987)
- Longqi Liu (ORCID: https://orcid.org/0000-0002-5828-5542)
- Xialin Chen (ORCID: https://orcid.org/0000-0001-7589-7957)
- Shuangfeng Zhang
- Hongmei Zhu (ORCID: https://orcid.org/0000-0003-2380-9753)
- Wentao Zhou
- Youwei Ai (ORCID: https://orcid.org/0000-0002-2698-623X)
- Fangzheng Liu (ORCID: https://orcid.org/0009-0008-4016-572X)
- Songbai Gui (ORCID: https://orcid.org/0000-0002-3638-2018)
- Mengjiao Gao (ORCID: https://orcid.org/0000-0003-0143-4073)
- Lei Han (ORCID: https://orcid.org/0000-0002-7535-7915)
- Hongying Ye (ORCID: https://orcid.org/0000-0002-6932-3145)
- Xiaochan Wei
- Wentao Wu (ORCID: https://orcid.org/0000-0001-7621-2198)
- Yongji Tian (ORCID: https://orcid.org/0000-0001-9915-8630)
- Yuqi Miao (ORCID: https://orcid.org/0000-0002-3513-3685)
- Wei Li (ORCID: https://orcid.org/0000-0003-3364-8690)
- Peng Zhang (ORCID: https://orcid.org/0000-0002-6218-1885)
- Si Li (ORCID: https://orcid.org/0000-0001-9291-9804)
- Zhiming Liu (ORCID: https://orcid.org/0000-0002-4030-862X)
- Jian Gong (ORCID: https://orcid.org/0000-0003-3273-2778)
- Zhenhua Chen (ORCID: https://orcid.org/0000-0002-0161-0236)
- Shuping Han
- Di Wu (ORCID: https://orcid.org/0000-0003-3135-0567)
- Taotao Pan
- Xuelian Sun
Institutions
- BGI Group (China) (CN)
- McGovern Institute for Brain Research (US)
- Capital Medical University (CN)
- Chinese Academy of Sciences (CN)
- Fudan University (CN)
- National Institute of Biological Sciences, Beijing (CN)
- Beijing Tian Tan Hospital (CN)
- Center for Excellence in Brain Science and Intelligence Technology (CN)
- Beijing Graphene Institute (CN)
- Chinese Institute for Brain Research (CN)
- Institute of Genetics and Developmental Biology (CN)
- Beijing Radiation Center (CN)
- Beijing Children’s Hospital (CN)
- Huashan Hospital (CN)
- University of Chinese Academy of Sciences (CN)
- BGI Research (CN)
Publication Details
- Journal
- Science Translational Medicine
- Published
- 2024-12-18
- DOI
- https://doi.org/10.1126/scitranslmed.adn6763
- Citations
- 10
- Primary Topic
- Pituitary Gland Disorders and Treatments
- Type
- article
- Field-Weighted Citation Impact
- 3.58