作为诱饵受体，可溶性ST2 (sST2) 干扰炎症细胞因子白细胞介素(IL)-33 的功能。结直肠癌(CRC)细胞中降低sST2表达，通过 IL-33 介导的生物过程促进肿瘤生长。在本研究中，我们发现缺氧减少了 CRC 细胞中的 sST2 表达，并探讨了相关的分子机制，包括在缺氧 CRC 细胞中 ST2 基因转录的关键调控因子的表达。此外，使用对缺氧响应的小鼠CRC细胞工程表达sST2，研究了在缺氧肿瘤区域恢复sST2表达对恶性进展的影响。我们的结果表明，缺氧诱导的核内IL-33 增加干扰了GATA3 对 ST2 基因转录的转录活性。最重要的是，缺氧肿瘤区域的sST2恢复矫正了炎症微环境，抑制了肿瘤生长和肺转移。这些结果表明，针对缺氧肿瘤区域的 sST2 的策略可能是治疗恶性CRC有效的方法。

As a decoy receptor, soluble ST2 (sST2) interferes with the function of the inflammatory cytokine interleukin (IL)-33. Decreased sST2 expression in colorectal cancer (CRC) cells promotes tumor growth via IL-33-mediated bioprocesses in the tumor microenvironment. In this study, we discovered that hypoxia reduced sST2 expression in CRC cells and explored the associated molecular mechanisms, including the expression of key regulators of ST2 gene transcription in hypoxic CRC cells. In addition, the effect of the recovery of sST2 expression in hypoxic tumor regions on malignant progression was investigated using mouse CRC cells engineered to express sST2 in response to hypoxia. Our results indicated that hypoxia-dependent increases in nuclear IL-33 interfered with the transactivation activity of GATA3 for ST2 gene transcription. Most importantly, hypoxia-responsive sST2 restoration in hypoxic tumor regions corrected the inflammatory microenvironment and suppressed tumor growth and lung metastasis. These results indicate that strategies targeting sST2 in hypoxic tumor regions could be effective for treating malignant CRC.