CD 44 and Metastasis

After metastatic dissemination of tumor cells, therapeutic approaches frequently are no longer curative. Partly this is due to our ignorance of tumor progression, which hampers the development of new therapeutic concepts. After many years of research to unravel the processes of metastasis formation, the finding that expression of a single molecule, CD44v, suffices to initiate tumor cell dissemination in the rat was completely unexpected. Since metastasis formation is a multistep process, it is supposed that CD44v is a regulatory gene product whose expression possibly initiates a cascade of events. It is unlikely that tumor cells establish a biological program by series of mutations and selection steps. Yet, reactivation of developmentally expressed genes has frequently been noted during tumor progression. In fact, expression of CD44v is found on many epithelial cells and, in particular, hematopoetic precursor cells during ontogeny. In addition, the program of lymphocyte activation has much in common with the lymphatic spread of tumor cells. Therefore, we speculate that unravelling these physiological processes may supply valuable information regarding tumor progression. First clinical studies have proven that expression of CD 44v is not restricted to the rat model. Although a correlation between expression of CD44v and tumor cell dissemination was not observed with all human malignancies evaluated so far, a clear linkage between malignant phenotype and expression of CD44v was noted in some tumor systems like, e.g., colon carcinoma. Furthermore, especially with mammary carcinomas, expression of CD44v proved to be of utmost prognostic relevance. In view of these findings, diagnostic and therapeutic utilization of CD44v-specific antibodies and effector cells should be taken into consideration.