Contribution of the Receptor/Ligand Interaction Between CD44 and Osteopontin to Formation of Breast Cancer Metastases
Abstract
Cancer is characterized by dysregulated growth control, overcoming of cellular aging, and metastasis formation. The latter distinguishes malignant tumors from benign tumors and is mediated by groups of molecules called homing receptors, cytokines, and proteinases. Expression of these molecules on tumor cells determines when and where particular types of cancer spread. The physiologic role of the relevant receptors, cytokines, and proteases in the healthy, cancer-free organism has been incompletely understood. We have studied a homing receptor, known as CD44, and its ligand. the cytokine osteopontin. In host defense, CD44 and osteopontin play key roles in mediating delayed types of immune response that are important in tuberculosis, organ transplantation, and many forms of vaccination. Macrophages are the cells that mainly determine whether an immune reaction will have delayed (cell-mediated) or acute (antibody-mediated) characteristics, and osteopontin and CD44 direct macrophages to the former. The engagement of CD44 by osteopontin also induces macrophage migration, a mechanism that metastatic tumors may utilize in the process of dissemination. We have found that other gene products that contribute to dissemination of cancerous cells similarly contribute to host defenses, and we conclude that metastasis genes are developmentally non-essential genes which physiologically mediate stress responses. inflammation, wound healing, and blood vessel formation.
Document Details
- Document Type
- Technical Report
- Publication Date
- Jul 01, 2002
- Accession Number
- ADA407640
Entities
People
- Georg F. Weber
Organizations
- Tufts Medical Center