A Metastasis Trap for Breast Cancer
Abstract
Here we report the results of our pilot studies to find new approaches to fight the propensity of breast cancer cells to metastasize. Since the latter depends on increased motility secondary to degradation of extracellular matrix (ECM) we studied the inhibitors of matrix metalloproteinases (MMPs). MMPs activate proteolysis of ECM and are implicated in cancer and metastasis. As a model of cell motility we used Xenopus laevis embryos because their germ cell layers undergo extensive movements in the gastrula stage of development. Injection of a synthetic mRNA encoding an inhibitor of MMPs, Xtimp3, led to shortening of the embryonic anterior-posterior axis and to eye defects, indicating defect of motility. We concluded that Xtimp3 interferes with cell motility. Similar movement defects are produced by Wnt oncogen receptors of Frizzled family. We tested for the involvement of a Frizzled receptor, Xfz8, in carcinogenesis and found that Xfs8 triggered apoptosis in gastrulating Xenopus embryos. Induction of apoptosis by Xfz8 required the cytoplasmic tail of the receptor (Appendix, Figure 3) and depended on the activation of c-jun N-terminal kinases. It occurred in Beta-catenin and convergent extension pathway-independent manner. These results raise the possibility that Wnt/Frizzled signaling may control tumor growth by regulating apoptosis in cancer cells.
Document Details
- Document Type
- Technical Report
- Publication Date
- May 01, 2002
- Accession Number
- ADA405315
Entities
People
- Mikhail Y. Lisovsky