Department of Biochemistry, The Jikei University School of Medicine, 3-25-8 Nishi-shinbashi, Minato-ku, Tokyo 105-8461, Japan.
Division of Cellular Signaling, National Cancer Center Research Institute, Tokyo, Japan.
Cancer Treat Res Commun. 2021;27:100332. doi: 10.1016/j.ctarc.2021.100332. Epub 2021 Feb 9.
Metastatic progression is the leading cause of mortality in breast cancer. However, molecular mechanisms that govern this process remain unclear. In this study, we found that carbonic anhydrase 13 (CA13) plays a potential role in suppressing bone metastasis. iRFP713-labeled iCSCL-10A (iRFP-iCSCL-10A) breast cancer cells, which exhibit the hallmarks of cancer stem cells, exerted the ability of bone metastasis in hind legs after 5-week injections, whereas no metastasis was observed in control iRFP713-labeled MCF-10A (iRFP-MCF10A) cells. Transcriptome analysis indicated that the expression of several genes, including metabolism-related CA13, was reduced in bone metastatic iRFP-iCSCL-10A cells. In vitro and in vivo analyses demonstrated that overexpression of CA13 in iRFP-iCSCL-10A cells suppressed migration, invasion, and bone metastasis, together with the reduction of VEGF-A and M-CSF expression. Furthermore, we found that breast cancer patients with a low CA13 expression had significantly shorter overall survival and disease-free survival rates compared to those with higher CA13 expression. These findings suggest that CA13 may act as a novel prognostic biomarker and would be a therapeutic candidate for the prevention of bone metastasis in breast cancer.
转移进展是乳腺癌死亡的主要原因。然而，控制这一过程的分子机制仍不清楚。在这项研究中，我们发现碳酸酐酶 13（CA13）在抑制骨转移中发挥潜在作用。经过 5 周注射后，具有癌症干细胞特征的 iRFP713 标记的 iCSCL-10A（iRFP-iCSCL-10A）乳腺癌细胞在后腿具有骨转移的能力，而对照的 iRFP713 标记的 MCF-10A（iRFP-MCF10A）细胞则没有转移。转录组分析表明，包括代谢相关 CA13 在内的几个基因的表达在骨转移的 iRFP-iCSCL-10A 细胞中降低。体外和体内分析表明，iRFP-iCSCL-10A 细胞中 CA13 的过表达抑制迁移、侵袭和骨转移，同时降低 VEGF-A 和 M-CSF 的表达。此外，我们发现 CA13 表达较低的乳腺癌患者的总生存率和无病生存率明显低于 CA13 表达较高的患者。这些发现表明 CA13 可能作为一种新的预后生物标志物，并可能成为预防乳腺癌骨转移的治疗候选物。
