Back to Search
Start Over
Dedifferentiation of neuroendocrine carcinoma of the uterine cervix in hypoxia
- Source :
- Biochemical and biophysical research communications. 524(2)
- Publication Year :
- 2019
-
Abstract
- Neuroendocrine carcinoma of small cell type (SCNEC) is a rare pathological subtype in cervical cancer, which has a worse prognosis than other histological cell types. Due to its low incidence and the lack of experimental platforms, the molecular characteristics of SCNEC in the cervix remain largely unknown. Using the cancer tissue-originated spheroid (CTOS) method—an ex vivo 3D culture system that preserves the differentiation status of the original tumors—we established a panel of CTOS lines of SCNEC. We demonstrated that xenograft tumors and CTOSs, respectively, exhibited substantial intra-tumor and intra-CTOS variation in the expression levels of chromogranin A (CHGA), a neuroendocrine tumor marker. Since hypoxia affects differentiation in various tumors and in stem cells, we also investigated how hypoxia affected neuroendocrine differentiation of SCNEC of the uterine cervix. In the CTOS line cerv21, hypoxia suppressed expression of the neuroendocrine markers CHGA and synaptophysin (SYP). Flow cytometry analysis using CD99 (a membrane protein marker of SCNEC) revealed decreased CD99 expression in a subset of cells under hypoxic conditions. These expression changes were attenuated by HIF-1α knockdown, and by a Notch inhibitor, suggesting that these molecules played a role in the regulation of neuroendocrine differentiation. The examined SCNEC markers were suppressed under hypoxia in multiple CTOS lines. Overall, our present results indicated that neuroendocrine differentiation in SCNEC of the uterus is a variable phenotype, and that hypoxia may be one of the factors regulating the differentiation status.
- Subjects :
- 0301 basic medicine
Cell type
Biophysics
Uterine Cervical Neoplasms
Cervix Uteri
Biochemistry
Neuroendocrine differentiation
03 medical and health sciences
Mice
0302 clinical medicine
medicine
Tumor Cells, Cultured
Animals
Humans
Carcinoma, Small Cell
Molecular Biology
Tumor marker
biology
Chromogranin A
Cancer
Cell Biology
Hypoxia (medical)
Cell Dedifferentiation
medicine.disease
Carcinoma, Neuroendocrine
030104 developmental biology
030220 oncology & carcinogenesis
biology.protein
Synaptophysin
Cancer research
Tumor Hypoxia
Female
medicine.symptom
Stem cell
Subjects
Details
- ISSN :
- 10902104
- Volume :
- 524
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Biochemical and biophysical research communications
- Accession number :
- edsair.doi.dedup.....07af3de14191195a37a3681dbb8efc74