Department of Histology and Embryology, Akdeniz University, Antalya, Turkey.
Faculty of Medicine, Department of Anatomy, TOBB University of Economics and Technology, Ankara, Turkey.
Biotech Histochem. 2024 Feb;99(2):76-83. doi: 10.1080/10520295.2024.2305114. Epub 2024 Jan 31.
Three genes are associated with cerebral cavernous malformations (CCMs): and . These genes participate in microvascular angiogenesis, cell-to-cell junctions, migration and apoptosis. We evaluated the expression in vivo of CCM genes in primary tumors and metastastases in a murine model of metastatic breast carcinoma. We used cell lines obtained from metastasis of 4T1, 4TLM and 4THM breast cancer to liver and heart. These cells were injected into the mammary ridge of Balb/C female mice. After 27 days, the primary tumors, liver and lung were removed and CCM proteins were assessed using immunohistochemistry and western blot analysis. CCM proteins were expressed in primary tumor tissues of all tumor-injected animals; however, no CCM protein was expressed in metastatic tumor cells that migrated into other tissues. CCM proteins still were observed in the lung and liver tissue cells. Our findings suggest that CCM proteins are present during primary tumor formation, but when these cells develop metastatic potential, they lose CCM protein expression. CCM protein expression was lost or reduced in metastatic tissues compared to the primary tumor, which indicates that CCM proteins might participate in tumorigenesis and metastasis.
三个基因与脑动静脉畸形（CCM）有关： 和 。这些基因参与微血管生成、细胞-细胞连接、迁移和凋亡。我们在转移性乳腺癌的小鼠模型中评估了 CCM 基因在原发肿瘤和转移灶中的体内表达。我们使用来自 4T1、4TLM 和 4THM 乳腺癌转移的细胞系注射到 Balb/C 雌性小鼠的乳腺嵴。27 天后，切除原发肿瘤、肝脏和肺，并使用免疫组织化学和 Western blot 分析评估 CCM 蛋白。所有注射肿瘤的动物的原发肿瘤组织中均表达 CCM 蛋白；然而，迁移到其他组织的转移性肿瘤细胞中未表达 CCM 蛋白。CCM 蛋白仍存在于肺和肝组织细胞中。我们的发现表明，CCM 蛋白在原发肿瘤形成时存在，但当这些细胞具有转移潜能时，它们会失去 CCM 蛋白表达。与原发肿瘤相比，转移组织中的 CCM 蛋白表达缺失或减少，这表明 CCM 蛋白可能参与肿瘤发生和转移。
