作者: Yamamoto, Mao ; Yashiro, Narumi ; Taniguchi, Anri ; Tamura, Moemi ; Shimomura, Nanami ; Takai, Miwa ; Tsujiuchi, Toshifumi ; Nagano, Shion ; Kusumoto, Yuka

Hypoxia contributes to tumor progression, promoting cancer cell motility, invasion and metastasis. Lysophosphatidic acid (LPA) receptors are implicated in the pathogenesis of cancer. In this study, we investigated the role of LPA receptor signaling in modulating malignant behavior under hypoxic conditions (1 % O₂) in lung cancer cells. We generated highly migratory A549-R12 cells from the parental lung cancer A549 cells for this purpose. LPAR1 and LPAR2 expression levels were lower in both A549 and A549-R12 cells cultured at 1 % O₂ compared to those cultured at 21 % O₂, while LPAR3 expression remained unchanged between the two cell lines. Cell motility increased in both A549 and A549-R12 cells cultured at 1 % O₂. Notably, A549-R12 cells exhibited greater motility under 1 % O₂ conditions than A549 cells. Treatment with AM966 (an LPA₁ antagonist) and (2S)-OMPT (an LPA₃ agonist) further increased the motility of A549-R12 cells, while GRI-977143 (an LPA₂ agonist) decreased their motility. Moreover, the invasion activity of A549-R12 cells was higher than that of A549 cells, with 1 % O₂ conditions significantly enhancing A549-R12 cell invasion. AM966 and (2S)-OMPT stimulated, whereas GRI-977143 inhibited, the invasion of A549-R12 cells. In the presence of LPA, cell viability to cisplatin (CDDP) was higher in A549-R12 cells cultured at both 21 % and 1 % O₂ compared to A549 cells. These results suggest that LPA receptor signaling plays a key role in regulating malignant progression in highly migratory lung cancer cells under hypoxic conditions.

2025-05-01·Advances in biological regulation

Cellular responses to low nutrient conditions via activation of lysophosphatidic acid (LPA) receptor signaling in gastric cancer cells

Article

作者: Yamamoto, Mao ; Tamura, Moemi ; Yashiro, Narumi ; Nagano, Shion ; Tsujiuchi, Toshifumi ; Takai, Miwa ; Kusumoto, Yuka ; Taniguchi, Anri

In the center of the solid tumor, abnormal vascular architecture impedes sufficient blood supply, leading to continuous hypoxia and nutrient deprivation for the tumor cells. Lysophosphatidic acid (LPA) receptor signaling is known to drive a range of malignant behaviors in cancer cells. This study aimed to explore the impact of LPA receptors on cellular functions in gastric cancer AGS cells cultured under low nutrient conditions. When AGS cells were cultured in media containing low glucose (2000 mg/L), low glutamine (1 mM), or low amino acids (50 % content), LPA receptor expression levels were significantly altered. The growth activity of AGS cells cultured in low glucose- and low amino acid-containing media was suppressed by LPA. Conversely, LPA increased the growth activity of AGS cells cultured in low glutamine-containing media. AGS cell motility increased under low glucose and low glutamine conditions, while low amino acid conditions decreased cell motility. Additionally, the viability of AGS cells in response to cisplatin (CDDP) was enhanced under low glucose, low glutamine, and low amino acid conditions. The motility and viability of AGS cells in response to CDDP were significantly increased by AM966 (LPA₁ antagonist), GRI-977143 (LPA₂ agonist) and (2S)-OMPT (LPA₃ agonist). These results suggest that LPA receptor signaling is significantly implicated in regulating malignant properties in AGS cells under low nutrient conditions.

2025-05-01·Advances in biological regulation

Lysophosphatidic acid (LPA) receptor signaling modulates cellular functions of colon cancer cells under cobalt chloride-induced hypoxic conditions

Article

作者: Yashiro, Narumi ; Yamamoto, Mao ; Nagano, Shion ; Shimomura, Nanami ; Takai, Miwa ; Tsujiuchi, Toshifumi ; Taniguchi, Anri ; Tamura, Moemi ; Kusumoto, Yuka

In the tumor microenvironment (TME), hypoxia is critical in promoting tumor invasiveness and progression. Cobalt chloride (CoCl₂) mimics hypoxia by inducing comparable cellular responses. Lysophosphatidic acid (LPA) receptors (LPA₁ to LPA₆) play key roles in regulating cancer cell functions. In this study, we investigated the impact of LPA receptor signaling on malignant properties of colon cancer DLD-1 cells under hypoxic condition induced by CoCl₂. LPAR1 and LPAR2 expression levels were elevated in DLD-1 cells treated with CoCl₂. CoCl₂ treatment also stimulated DLD-1 cell motility. This enhanced motility induced by CoCl₂ was reduced with LW6 (HIF-1 inhibitor). Additionally, the motility of CoCl₂-treated DLD-1 cells was suppressed by AM966 (LPA₁ antagonist) and enhanced by GRI-977143 (LPA₂ agonist). Conversely, CoCl₂ treatment decreased DLD-1 cell invasion. While AM966 further inhibited cell invasion, GRI-977143 elevated it. The cell viability to fluorouracil (5-FU) was higher in CoCl₂-treated DLD-1 cells. This increased viability to 5-FU was further enhanced by both AM966 and GRI-977143. When CoCl₂-treated DLD-1 cells were cultured in low-glucose media, LPAR1 expression was upregulated compared to high-glucose media, while LPAR2 expression was downregulated. Additionally, motility and invasion in CoCl₂-treated DLD-1 cells were further stimulated under low-glucose conditions. These results suggest that LPA receptor signaling contributes to the malignant potential of DLD-1 cells in a hypoxic environment induced by CoCl₂ treatment.

100 项与 AM966 相关的药物交易

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