Stem-like tumor cells involved in heterogeneous vasculogenesis in breast cancer.
Endocr Relat Cancer
; 27(1): 23-39, 2020 01.
Article
en En
| MEDLINE
| ID: mdl-31705798
ABSTRACT
Sorafenib, a small-molecule tyrosine kinase inhibitor with antiangiogenic activity, has been used in liver cancer and kidney cancer treatments. However, clinical trials with sorafenib for breast cancer were stopped in phase III due to limited efficacy. The existence of heterogeneous vasculatures involving tumor cells, such as vessel-like structures formed by vasculogenic mimicry and mosaic vessels, and their resistance to antiangiogenic therapy are thought to be a possible reason for failure of sorafenib therapy. Nevertheless, the features and mechanism of vasculogenesis by tumor cells remain unclear. In the present study, we found that breast cancer stem-like cells (BCSLCs, ALDH1+ cells) were involved in vasculogenic mimicry and mosaic vessel formation in triple-negative breast cancer tissues. Further, only ALDH1+ BCSLCs sorted from MDA-MB-231 could exhibit the tube formation and angiogenesis ability. Sorafenib could inhibit vascularization from endothelial cells rather than that from ALDH1+ cells. α-SMA was identified as a key molecule in vascular formation of BCSLCs. Mechanistically, HIF-1α enhanced the mRNA and protein levels of α-SMA by binding to the HRE element in the promoter directly and meanwhile increased the BCSLCs population. Interestingly, pigment epithelium-derived factor (PEDF), an endogenous angiogenesis inhibitor, could inhibit both endothelial cell-derived and tumor cell-derived angiogenesis by downregulating HIF-1α in breast cancer. Our finding clarified the possible reason for the poor outcome of anti-angiogenesis therapy and PEDF may have the therapeutic potential.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Células Madre Neoplásicas
/
Células Endoteliales
/
Neoplasias de la Mama Triple Negativas
/
Sorafenib
/
Neovascularización Patológica
Tipo de estudio:
Prognostic_studies
Límite:
Animals
/
Female
/
Humans
Idioma:
En
Revista:
Endocr Relat Cancer
Asunto de la revista:
ENDOCRINOLOGIA
/
NEOPLASIAS
Año:
2020
Tipo del documento:
Article
País de afiliación:
China