Heterogenous chemosensitivity of a panel of organoid lines derived from small cell neuroendocrine carcinoma of the uterine cervix

Small cell neuroendocrine carcinoma (SCNEC) of the uterine cervix is a rare disease with a poor prognosis. The lack of established disease models has hampered therapy development. We generated a panel of cancer tissue-originated spheroid (CTOS) lines derived from SCNEC of the uterine cervix using a...

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Published in:Human cell : official journal of Human Cell Research Society 2021-05, Vol.34 (3), p.889-900
Main Authors: Tanaka, Mie, Kondo, Jumpei, Kaneko, Kensuke, Endo, Hiroko, Onuma, Kunishige, Coppo, Roberto, Masuda, Masamune, Kamiura, Shoji, Yoshino, Kiyoshi, Ueda, Yutaka, Kakeya, Hideaki, Kimura, Tadashi, Inoue, Masahiro
Format: Article
Language:English
Subjects:
Biomedical and Life Sciences
Cell Biology
Cervix
DNA microarrays
Drug development
Gynecology
Irinotecan
Life Sciences
Neuroendocrine tumors
Oncology
Organoids
Rare diseases
Reproductive Medicine
Research Article
Stem Cells
Surgery
Uterine cancer
Uterus
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Summary:Small cell neuroendocrine carcinoma (SCNEC) of the uterine cervix is a rare disease with a poor prognosis. The lack of established disease models has hampered therapy development. We generated a panel of cancer tissue-originated spheroid (CTOS) lines derived from SCNEC of the uterine cervix using a method based upon cell–cell contact throughout the preparation and culturing processes. Using 11 CTOS lines, we assessed the sensitivity of various drugs used in clinical practice. Drug sensitivity assays revealed significant heterogeneous inter-CTOS chemosensitivity. Microarray analyses were then performed to identify sensitivity-related gene signatures. Specific gene sets were identified which likely contribute to the sensitivity to the tested drugs. We identified a line (Cerv54) that was exceptionally sensitive to irinotecan. Cerv54 had increased levels of CES1, which catalyzes the conversion of irinotecan to the active form, SN38, although in Cerv54 cells, SN38 was undetectable, CES1 expression and activity were markedly low compared to the liver, and a CES1 inhibitor had no effect on irinotecan sensitivity. These results suggested a novel irinotecan mode of action in Cerv54. Our CTOS lines may be useful for understanding the variation and mechanism of drug sensitivity, contributing to the understanding and development of chemotherapeutic drugs.
ISSN:1749-0774
0914-7470
1749-0774
DOI:10.1007/s13577-021-00511-5