Lysophosphatidic acid (LPA) receptor-mediated signaling regulates hypoxia-induced biological functions of lymphatic endothelial cells

被引:2
作者
Yamamoto, Mao [1 ]
Takai, Miwa [1 ]
Yashiro, Narumi [1 ]
Hayasaka, Haruko [2 ]
Tsujiuchi, Toshifumi [1 ]
机构
[1] Kindai Univ, Fac Sci & Engn, Dept Life Sci, Div Mol Oncol, 3-4-1 Kowakae, Higashiosaka, Osaka 5778502, Japan
[2] Kindai Univ, Fac Sci & Engn, Dept Life Sci, Lab Immune Mol Funct, 3-4-1 Kowakae, Higashiosaka, Osaka 5778502, Japan
关键词
Lysophosphatidic acid; LPA receptors; Hypoxia; Lymphatic endothelial cells; Tube formation; TUMOR HYPOXIA; CANCER;
D O I
10.1016/j.bbrc.2024.149982
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
The tumor microenvironment is an extremely complex composed of cancer cells and various non-cancer cells, including lymphatic endothelial cells. Lysophosphatidic acid (LPA) receptors (LPA1 to LPA6) activate a variety of malignant properties in human malignancies. In the present study, we examined the roles of LPA receptormediated signaling in biological responses of lymphatic endothelial SVEC4-10 cells induced by hypoxia. Lpar1, Lpar2 and Lpar3 expressions were decreased in SVEC4-10 cells cultured at hypoxic conditions (1 % O2). LPA had no impact on the cell growth activity of SVEC4-10 cells in 21 % O2 culture conditions. Conversely, the cell growth activity of SVEC4-10 cells in 1 % O2 culture conditions was reduced by LPA. The cell motile activity of SVEC4-10 cells was elevated by 1 % O2 culture conditions. GRI-977143 (LPA2 agonist) and (2S)-OMPT (LPA3 agonist) stimulated SVEC4-10 cell motility as well as AM966 (LPA1 antagonist). In tube formation assay, the tube formation of SVEC4-10 cells in 1 % O2 culture conditions was markedly increased, in comparison with 21 % O2. GRI-977143 and (2S)-OMPT elevated the tube formation of SVEC4-10 cells. Furthermore, the tube formation of SVEC4-10 cells was increased by AM966. These results suggest that LPA receptor-mediated signaling contributes to the modulation of hypoxic-induced biological functions of lymphatic endothelial cells.
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页数:6
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