Bryostatins are macrolactones isolated from marine organisms. Of the more than 20 known bryostatins, bryostatin-1 is the best characterized. Bryostatin-1 potently inhibits tumor growth, metastasis, and angiogenesis in vitro and in vivo, and it is currently being evaluated in clinical studies in US for its therapeutic potential against various types of cancer.However, the mechanisms involved in tumor suppression, especially metastasis inhibition, of bryostatins remain to be elucidated.

On November 1^st, Cancer Research published the the latest research results of Dr. Xin XIE’s group from National Center for Drug Screening, Shanghai Institute of Materia Medica.In this paper, the possible pathway involved in bryostatin-induced metastasis inhibition was brought to light.

The chemokine receptor CXCR4 and its ligand, SDF-1, play important roles in hematopoiesis regulation, lymphocyte activation and trafficking, as well as in developmental processes including organogenesis, vascularization, and embryogenesis. CXCR4 is also involved in the growth and metastasis of various types of cancers. Many types of human cancer over-express CXCR4, and cancer cells with higher levels of CXCR4 show greater incidence of metastasis., Together with colleagues, Xing HE, a graduate student from Dr.Xin XIE’s group, discovered that bryostatins could inhibit chemotaxis and calcium mobilization mediated by SDF-1/CXCR4. However, the inhibitory effect is not due to direct blockade of the SDF-1 and CXCR4 interaction. Further studies indicate that bryostatins can induce CXCR4 desensitization and internalization to cause the termination of signal transduction of SDF-1/CXCR4. And the desensitization and internalization of CXCR4 are mediated by activation of PKCs. In this study, we reported for the first time the involvement of bryostatins in the SDF1/CXCR4 signaling process. Our results indicate bryostatins inhibit cancer cell metastasis by inducing surface CXCR4 desensitization and internalization.

The Bryostatins used in this study were provided by Dr. Yanghua YI’s group from the Research Center for Marine Drugs, School of Pharmacy, Second Military Medical University

 

 

 

　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　　  (National Center for Drug Screening　 Xin XIE)