ABSTRACT
Three genes are associated with cerebral cavernous malformations (CCMs): CCM1, CCM2 and CCM3. 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.
Acknowledgments
Our study was supported by Akdeniz University Scientific Research Projects, project no. TYL-2015-1036 and is based on the Master of Science thesis of Mansur Cici. Some parts of this study were presented in the XIII National Congress of Histology and Embryology and the 22nd Electron Microscopy Congress (EMK 2015) as poster presentations. We thank Prof. Dr. Nuray ERİN for providing the cell lines.
Disclosure statement
The authors declare no conflict of interest.