Involvement of CD44, a Molecule with a Thousand Faces, in Cancer Dissemination

Cancer progression and metastasis are complex processes associated with multiple and highly organized sequential steps that are both well coordinated and organ selective. The interplay between chemokines, cytokines, growth factors, cell-bound or tissue-bound enzymes, adhesion and homing molecules, as well as apoptosis-promoting and survival-inducing signals, determines the tumor fate for life or death. This chapter provides a comprehensive understanding of the sophisticated biological networks for developing novel therapeutic strategies. It explores the involvement of CD44 in lymph node colonization by LB cells. CD44 isoforms support the local growth and the metastatic spread of LB cell lymphoma, DA3 mammary adenocarcinoma, and many other hematological and solid tumors. The study presents examples to show that standard CD44, rather than its variants, enhances tumor progression. A certain combination of conditions dictates very high affinity of CD44 to its tissue ligand (an example prostate cancer), resulting in tumor arrest in the local growth and a minimal metastatic phase. Hence, the CD44 structure-function relationship must be separately analyzed in each tumor, and accordingly the therapeutic suit should be tailored.