Ets 1 is Expressed in Capillary Blood Vessels but Not in Lymphatics

Little is known about the mechanisms that regulate lymphangiogenesis and, in particular, about regulation at the transcriptional level. To determine whether parallels exist in the mechanisms of angiogenesis and lymphangiogenesis, the expression of the Ets 1 transcription factor (which has previously been shown to be involved in angiogenesis) was examined in two transgenic mouse lines, namely RipVEGF-C mice (which develop lymphatic capillaries ectopically around islets of Langerhans) and Rip1Tag2 mice (which develop insulinomas that are not lymphangiogenic). Crossing the two lines results in double transgenic mice that develop lymphatics around insulinomas, which in turn promotes metastasis to regional lymph nodes. By immunohistochemistry, it was found that, in contrast to blood vessels, lymphatic vessels in wild-type and transgenic mice did not express Ets 1. Immunohistochemical staining for matrix metalloproteinase (MMP)-2 and MMP-9 as well as membrane type 1-MMP (MT1-MMP/MMP-14), all of which are encoded by known or potential Ets 1 target genes, showed the same cellular distribution as Ets 1. These findings suggest that the transcriptional regulatory mechanisms of lymphangiogenesis differ from those involved in angiogenesis. Furthermore, if proteases are involved in lymphangiogenesis, these observations suggest that they are different from those considered to be important for blood vessel formation.