EPHB3

Abstract: The EPH family is the largest subfamily of receptor protein tyrosine kinases, consisting of the EPHA and EPHB subgroups. Ephrin-B1, ephrin-B2, and ephrin-B3 are ligands of the EPHB subgroup and are encoded by the EFNB1, EFNB2, and EFNB3 genes, respectively. We have shown previously that EPHB2 transcripts are expressed in six small cell lung carcinoma (SCLC) cell lines. In this study, we examined the expression of EPHB1, EPHB2, EPHB3, EPHB4, and EPHB6 in 4 SCLC tumor specimens and 14 cell lines including 3 cell lines derived from these tumor specimens. To investigate whether potential autocrine loops of EPHB receptors and ephrin-B ligands exist in SCLC, the expression of EFNB1, EFNB2, and EFNB3 was also examined. Our data show that transcripts encoding multiple members of the EPHB subgroup and the ephrin-B subgroup are coexpressed in SCLC cell lines and tumors. These results suggest that the EPHB subgroup receptor kinases may modulate the biological behavior of SCLC through autocrine and/or juxtacrine activation by ephrin-B ligands that are expressed in the same or neighboring cells.

Abstract: The Eph subfamily of receptor tyrosine kinases and their membrane-anchored ephrin ligands mediate cell-cell contact signaling and are versatile regulators of cell migration and tissue patterning, which are often exploited by cancer cells during tumor progression. New evidence shows that prostate cancer cells use EphA2 and EphA4 receptors and ephrin-As to mediate homotypic contact inhibition of locomotion while co-opting ephrin-B2 on stromal cells through EphB3 and EphB4 receptors to propel migration. These processes could enhance cancer cell scattering from the primary tumor mass and promote unimpeded migration and invasion through the stromal space. The results provide another example in which Eph receptors are converted into pro-oncogenic proteins, contrary to their often-described tumor suppressor roles in normal tissues.