During mouse early development cell adhesion molecules are indispensable for the embryo organisation. A family of molecules probably involved in development is the transmembrane glycoprotein CD44 family, which exists in multiple isoforms. These are generated by alternative splicing of the pre‐mRNA, resulting in the enlargement of the extracellular part of the molecule. The standard form of CD44 is widely expressed in adult tissues and in embryos from day 9.5 post coitum onwards, while the numerous variant isoforms exhibit highly (...) specialised patterns of expression that are already in the egg cylinder at day 6.5 of development. In lymphohemopoiesis, specific variant isoforms also emerge at decisive differentiation stages. Although specific ligands for the variant region still await isolation, the highly organised expression of CD44 variant isoforms suggests they have a pivotal role in cellular interactions during early development, pattern formation and hemopoiesis. (shrink)

High‐molecular‐weight hyaluronan acts as a ligand of the tumor‐suppressive Hippo signal, whereas degradation of hyaluronan from a high‐molecular‐weight form to a low‐molecular‐weight forms by hyaluronidase 2 inhibits Hippo signal activation and thereby activates the pro‐oncogenic transcriptional coactivator yes‐associated protein (YAP), which creates a cancer‐predisposing microenvironment and drives neoplastic transformation of cells through both cell‐autonomous and non‐cell‐autonomous mechanisms. In fact, accumulation of low‐molecular‐weight hyaluronan in tissue stroma is observed in many types of cancers. Since inhibition of YAP activity suppresses tumor growth (...) in vivo, pharmacological intervention of the Hippo‐YAP signal is an attractive approach for future drug development. In this review, pharmacological intervention of excessive hyaluronan degradation as a novel approach for inhibition of the Hippo‐YAP signal is also discussed. Development of hyaluronidase inhibitors may provide novel therapeutic strategies for human malignant tumors. (shrink)