S100A4-dependent glycolysis promotes lymphatic vessel sprouting in tumor.
Angiogenesis
; 26(1): 19-36, 2023 02.
Article
em En
| MEDLINE
| ID: mdl-35829860
ABSTRACT
Tumor-induced lymphangiogenesis promotes the formation of new lymphatic vessels, contributing to lymph nodes (LNs) metastasis of tumor cells in both mice and humans. Vessel sprouting appears to be a critical step in this process. However, how lymphatic vessels sprout during tumor lymphangiogenesis is not well-established. Here, we report that S100A4 expressed in lymphatic endothelial cells (LECs) promotes lymphatic vessel sprouting in a growing tumor by regulating glycolysis. In mice, the loss of S100A4 in a whole body (S100A4-/-), or specifically in LECs (S100A4ΔLYVE1) leads to impaired tumor lymphangiogenesis and disrupted metastasis of tumor cells to sentinel LNs. Using a 3D spheroid sprouting assay, we found that S100A4 in LECs was required for the lymphatic vessel sprouting. Further investigations revealed that S100A4 was essential for the position and motility of tip cells, where it activated AMPK-dependent glycolysis during lymphatic sprouting. In addition, the expression of S100A4 in LECs was upregulated under hypoxic conditions. These results suggest that S100A4 is a novel regulator of tumor-induced lymphangiogenesis. Targeting S100A4 in LECs may be a potential therapeutic strategy for lymphatic tumor metastasis.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Células Endoteliais
/
Vasos Linfáticos
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Angiogenesis
Assunto da revista:
HEMATOLOGIA
Ano de publicação:
2023
Tipo de documento:
Article
País de afiliação:
China