Department of Radiation Oncology, Stanford University, Stanford, California 94305, USA.
Cancer Res. 2011 Jul 1;71(13):4423-31. doi: 10.1158/0008-5472.CAN-10-4157. Epub 2011 May 5.
Galectin-1 (Gal-1), a carbohydrate-binding protein whose secretion is enhanced by hypoxia, promotes tumor aggressiveness by promoting angiogenesis and T-cell apoptosis. However, the importance of tumor versus host Gal-1 in tumor progression is undefined. Here we offer evidence that implicates tumor Gal-1 and its modulation of T-cell immunity in progression. Comparing Gal-1-deficient mice as hosts for Lewis lung carcinoma cells where Gal-1 levels were preserved or knocked down, we found that tumor Gal-1 was more critical than host Gal-1 in promoting tumor growth and spontaneous metastasis. Enhanced growth and metastasis associated with Gal-1 related to its immunomodulatory function, insofar as the benefits of Gal-1 expression to Lewis lung carcinoma growth were abolished in immunodeficient mice. In contrast, angiogenesis, as assessed by microvessel density count, was similar between tumors with divergent Gal-1 levels when examined at a comparable size. Our findings establish that tumor rather than host Gal-1 is responsible for mediating tumor progression through intratumoral immunomodulation, with broad implications in developing novel targeting strategies for Gal-1 in cancer.
半乳糖凝集素-1（Gal-1）是一种糖结合蛋白，其分泌受缺氧的促进，通过促进血管生成和 T 细胞凋亡来促进肿瘤侵袭性。然而，肿瘤与宿主 Gal-1 在肿瘤进展中的重要性尚未确定。在这里，我们提供的证据表明，肿瘤 Gal-1 及其对 T 细胞免疫的调节在进展中起作用。比较 Gal-1 缺陷型小鼠作为保留或敲低 Gal-1 水平的 Lewis 肺癌细胞的宿主，我们发现肿瘤 Gal-1比宿主 Gal-1更能促进肿瘤生长和自发性转移。Gal-1 相关的增强生长和转移与其免疫调节功能有关，因为 Gal-1 表达对 Lewis 肺癌生长的益处在免疫缺陷小鼠中被消除。相比之下，通过微血管密度计数评估的血管生成在比较大小时，具有不同 Gal-1 水平的肿瘤之间相似。我们的发现确立了肿瘤而不是宿主 Gal-1 通过肿瘤内免疫调节来介导肿瘤进展，这对开发癌症中 Gal-1 的新型靶向策略具有广泛的意义。
