Magic roundabout, a tumor endothelial marker: Expression and signaling

Robo4 stabilizes the vascular network by inhibiting pathologic angiogenesis and endothelial hyperpermeability

“…Overexpression of Robo4 in endothelial cells, like Slit treatment, might prevent cell migration to angiogenic stimuli 7 . To test this possibility, we used adenoviral infection to overexpress Robo4 in endothelial cells.…”

Identification and angiogenic role of the novel tumor endothelial marker CLEC14A

“…Widespread expression of CLEC14A was seen in tumor vessels, but we again failed to detect CLEC14A on vessels in normal tissue (Figure 3a). The expression profile of CLEC14A was compared with that of the previously characterized TEM, ROBO4 (Huminiecki et al, 2002;Seth et al, 2005). Immunofluorescence analysis detected ROBO4 on vessels in many tumors but …”

Vascular Robo4 restricts proangiogenic VEGF signaling in breast

“…To determine SLIT function during mammary gland development, we initially focused on epithelial SLITs as a target-derived source because previous studies have reported directional migration of endothelial cells in response to exogenous or tumor-supplied SLIT protein (2,4,7,8). Only Slit2 and Slit3 are expressed by mammary epithelia (24); therefore, to evaluate the consequences of losing epithelial SLIT expression, we generated Slit2 −/− ;Slit3 −/− chimeric mammary outgrowths by transplantation because the Slit2 −/− mutation is perinatal lethal (Fig.…”

“…In contrast, ROBO4 binds SLITs at either very low affinity or not at all and likely requires a coreceptor, such as ROBO1 or a Syndecan, to signal (5,11,12). ROBO4 has been assigned the repellent functions of SLITs (7,8) and, more recently, an alternative role in countering the effects of vascular endothelial growth factor (VEGF) to provide vascular stabilization (13,14). One experimental variable that may be responsible for these contradictory findings is that many studies were performed in vitro using recombinant SLIT protein prepared in a variety of ways (2,5,6,8,13,15).…”

“…ROBO4 has been assigned the repellent functions of SLITs (7,8) and, more recently, an alternative role in countering the effects of vascular endothelial growth factor (VEGF) to provide vascular stabilization (13,14). One experimental variable that may be responsible for these contradictory findings is that many studies were performed in vitro using recombinant SLIT protein prepared in a variety of ways (2,5,6,8,13,15). Here, we circumvent the requirement for recombinant protein by taking a genetic approach to address the function of SLIT in a biological context using the mammary gland as a model system.…”