Yamamoto Mao, Takai Miwa, Yashiro Narumi, Taniguchi Anri, Tamura Moemi, Kusumoto Yuka, Nagano Shion, Tsujiuchi Toshifumi
Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan.
Division of Molecular Oncology, Department of Life Science, Faculty of Science and Engineering, Kindai University, 3-4-1, Kowakae, Higashiosaka, Osaka 577-8502, Japan.
Tissue Cell. 2024 Dec;91:102528. doi: 10.1016/j.tice.2024.102528. Epub 2024 Aug 23.
Solid tumors are formed by cancer cells and the surrounding non-cancer stromal cells under hypoxic conditions, collectively referred to as the tumor microenvironment (TME). Lysophosphatidic acid (LPA) receptor (LPA to LPA) signaling is crucial in regulating tumor progression. This study investigated the impact of LPA receptor signaling on the biological behaviors of colon cancer DLD-1 cells co-cultured with lymphatic endothelial SVEC4-10 cells under hypoxic conditions. Expression levels of LPAR1, LPAR2 and LPAR5 genes were significantly higher in DLD-1 cells co-cultured with SVEC4-10 cells compared to those cultured alone. Co-culturing with SVEC4-10 cells increased the motility of DLD-1 cells at 21 % O. LPA stimulated the motility of DLD-1 cells co-cultured with SVEC4-10 cells but had no effect on DLD-1 cells cultured alone. Furthermore, under 1 % O conditions, expression levels of LPAR1, LPAR2, and LPAR5 genes were markedly elevated in DLD-1 cells co-cultured with SVEC4-10 cells compared to 21 % O. The motility of DLD-1 cells co-cultured with SVEC4-10 cells was enhanced under 1 % O conditions. Viability of DLD-1 cells to fluorouracil (5-FU) in SVEC4-10 cell supernatants increased at 21 % O and decreased at 1 % O. Additionally, the LPA agonist GRI-977143 increased viability to 5-FU. These findings indicate that LPA receptor signaling plays a critical role in regulating the biological behaviors of DLD-1 cells co-cultured with SVEC4-10 cells under hypoxic conditions.
实体瘤是在缺氧条件下由癌细胞和周围的非癌基质细胞形成的，统称为肿瘤微环境（TME）。溶血磷脂酸（LPA）受体（LPA₁至LPA₅）信号传导在调节肿瘤进展中起关键作用。本研究调查了LPA受体信号传导对在缺氧条件下与淋巴管内皮SVEC4-10细胞共培养的结肠癌DLD-1细胞生物学行为的影响。与单独培养的DLD-1细胞相比，与SVEC4-10细胞共培养的DLD-1细胞中LPAR1、LPAR2和LPAR5基因的表达水平显著更高。在21%氧气浓度下，与SVEC4-10细胞共培养增加了DLD-1细胞的运动能力。LPA刺激了与SVEC4-10细胞共培养的DLD-1细胞的运动能力，但对单独培养的DLD-1细胞没有影响。此外，在1%氧气条件下，与21%氧气浓度相比，与SVEC4-10细胞共培养的DLD-1细胞中LPAR1、LPAR2和LPAR5基因的表达水平明显升高。在1%氧气条件下，与SVEC4-10细胞共培养的DLD-1细胞的运动能力增强。在21%氧气浓度下，DLD-1细胞对SVEC4-10细胞上清液中氟尿嘧啶（5-FU）的活力增加，在1%氧气浓度下则降低。此外，LPA激动剂GRI-977143增加了对5-FU的活力。这些发现表明，LPA受体信号传导在调节缺氧条件下与SVEC4-10细胞共培养的DLD-1细胞的生物学行为中起关键作用。
