Continuous endoglin (CD105) overexpression disrupts angiogenesis and facilitates tumor cell metastasis

Endoglin (CD105) is an auxiliary receptor for members of the TFG-β superfamily. Whereas it has been demonstrated that the deficiency of endoglin leads to minor and defective angiogenesis, little is known about the effect of its increased expression, characteristic of several types of cancer. Angiogenesis is essential for tumor growth, so high levels of proangiogenic molecules, such as endoglin, are supposed to be related to greater tumor growth leading to a poor cancer prognosis. However, we demonstrate here that endoglin overexpression do not stimulate sprouting or vascularization in several in vitro and in vivo models. Instead, steady endoglin overexpression keep endothelial cells in an active phenotype that results in an impairment of the correct stabilization of the endothelium and the recruitment of mural cells. In a context of continuous enhanced angiogenesis, such as in tumors, endoglin overexpression gives rise to altered vessels with an incomplete mural coverage that permit the extravasation of blood. Moreover, these alterations allow the intravasation of tumor cells, the subsequent development of metastases and, thus, a worse cancer prognosis.
This work was supported by the Ministerio de Economía y Competitividad of Spain (SAF2010-15881 AND SAF2013-45784-R), the Junta de Castilla y León (GR100), the Fundación Renal Iñigo Álvarez de Toledo, the Kidney Research Network REDINREN (RD06/0016/0013, RD12/0021/0032 and RD016/0009/0025) and the Instituto de Salud Carlos III (PI16/00460 and co-funded by FEDER). Furthermore, CO-I and EN-G are supported by a contract from the Ministerio de Economía y Competitividad of Spain, and CE-T is supported by a fellowship from the Fundación Miguel Casado San José.