Emerging role of endoglin (CD105) as a marker of angiogenesis with clinical potential in human malignancies.

Angiogenesis is crucial for tumor development and progression, and antiangiogenetic therapy represents a promising approach for cancer treatment. Thus, the in-depth understanding of the molecular mechanism(s) regulating angiogenesis, together with the characterization of molecules expressed by endothelial cells and involved in distinct steps of the angiogenetic process, will greatly improve the design of new and more effective therapeutic strategies in human malignancies. Endoglin (CD105), a cell membrane glycoprotein predominantly expressed on cellular lineages within the vascular system, and over-expressed on proliferating endothelial cells, is involved in blood vessels development and represents a powerful marker of neovascularization. CD105 binds several factors of the Transforming Growth Factor (TGF)-beta superfamily, a pleiotropic cytokine that regulates different cellular functions including proliferation, differentiation and migration. In human malignancies of different histotype, CD105 is highly expressed on endothelial cells of both peri- and intra-tumoral blood vessels, while it is weakly expressed or absent on neoplastic cells. This unique tissue distribution strongly suggests for a prognostic, diagnostic and therapeutic potential of CD105 in neoplastic diseases. In this review we will summarize the structural and functional features of CD105, as well as its tissue distribution in normal and neoplastic tissues. Furthermore, the practical implications of CD105 in human malignancies will also be discussed.