Hypothetical role of CEACAM1 in tumor lymphangiogenesis. Beside the already described expression of CEACAM1 in angiogenicly activated small blood vessels, CEACAM1 is also expressed in activated LECs and apparently prior to its expression in small tumor blood vessels. We hypothesize that the up-regulation of CEACAM1 in tumor-associated lymphatics is provided by factors of the VEGF family secreted by tumor cells (TC). Endothelial CEACAM1 in turn up-regulates the expression of potent lymphangiogenic factors VEGF-C and -D and their receptor VEGFR-3, as well as the expression of lymphatic marker podoplanin and prolymphatic transcription factor Prox1. VEGF-C and -D bind to VEGFR-3, which is predominantly expressed in LECs. Thus, we assume that (1) CEACAM1 upregulation in VECs during tumor angiogenesis leads to a partial reprogramming of VECs to LECs via interaction of Prox1 and VEGFR-3, and (2) CEACAM1 up-regulation in LECs supports tumor lymphangiogenesis via an autocrine loop, leading to increased expression of prolymphangiogenic factors VEGF-C, -D, and VEGFR-3.