Clinical significance of Gremlin 1 in cervical cancer and its effects on cancer stem cell maintenance.
Oncol Rep
; 35(1): 391-7, 2016 Jan.
Article
em En
| MEDLINE
| ID: mdl-26530461
ABSTRACT
Gremlin 1 is one of the bone morphogenetic protein (BMP) antagonists and is also related to differentiation in combination with BMPs and is associated with various types of diseases. Gremlin 1 is overexpressed in various types of human cancers and has been reported to play a role in cervical cancer oncogenesis. However, there is no report concerning the relationship between Gremlin 1 and cervical cancer stem cells (CSCs). The objective of the present study was to identify the clinical significance of Gremlin 1 in cervical cancer and its effects on CSC-like properties in vitro. Clinical samples were obtained. Gremlin 1 mRNA expression levels in the cervical cancer tissues were measured by RT-qPCR and assessed for correlation with their clinical prognosis [overall survival (OS), progression-free survival (PFS)] and with other prognostic factors. In vitro, cervical cancer, CaSki cells, exposed to Gremlin 1 (1,000 ng/ml) for 24 h were evaluated for expression of undifferentiated-cell markers (Nanog, Oct3/4, Sox2) by RT-qPCR, the population of ALDH-positive cells by flow cytometry and sphere-forming ability on a ultra-low attachment culture dish. Cervical cancer tissues from 104 patients were collected. A high mRNA expression level of Gremlin 1 was an independent poor prognostic factor of PFS but not of OS. A high mRNA expression level of Gremlin 1 was correlated with bulky (>4 cm) tumors. The Nanog mRNA expression level was significantly increased in the CaSki cells exposed to Gremlin 1 (P=0.0008) but not Oct3/4 and Sox2 mRNA expression levels. The population of ALDH-positive cells in the Gremlin 1-exposed cells was 1.41-fold higher compared with the control (P=0.0184). Sphere-forming ability was increased when 1,000 Gremlin 1-exposed cells were seeded (P=0.0379). In cervical cancer, it is suggested that Gremlin 1 may have a role in clinical recurrence and maintaining CSC-like properties.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células-Tronco Neoplásicas
/
Neoplasias do Colo do Útero
/
Peptídeos e Proteínas de Sinalização Intercelular
Tipo de estudo:
Prognostic_studies
Limite:
Adult
/
Aged
/
Female
/
Humans
/
Middle aged
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article