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To gain further insight into the mechanisms regulating the endothelial cell phenotype, we have compared the responses of lymphatic endothelial cells (LECs) and blood vascular endothelial cells (BECs) to vascular endothelial growth factors (VEGFs). VEGFR\u20103\u2010specific signals are sufficient for LEC but not BEC proliferation, as shown by the ability of the specific ligand VEGF\u2010C156S to stimulate cell cycle entry only in LECs. On the other hand, we found that VEGFR\u20103 stimulation did not induce LEC cell shape changes typical of VEGFR\u20102\u2010stimulated LECs, indicating receptor\u2010specific differences in the cytoskeletal responses. Genes induced via VEGFR\u20102 also differed between BECs and LECs: angiopoietin\u20102 (Ang\u20102) was induced via VEGFR\u20102 in BECs and LECs, but the smooth muscle cell (SMC) chemoattractant BMP\u20102 was induced only in BECs. Both BECs and LECs were able to promote SMC chemotaxis, but contact with SMCs led to down\u2010regulation of VEGFR\u20103 expression in BECs in a 3\u2010dimensional coculture system. This was consistent with the finding that VEGFR\u20103 is down\u2010regulated in vivo at sites of endothelial cell\u2010pericyte\/smooth muscle cell contacts. Collectively, these data show intrinsic cell\u2010specific differences of BEC and LEC responses to VEGFs and identify a pericellular regulatory mechanism for VEGFR\u20103 down\u2010regulation in endothelial cells.\u2014Veikkola, T., Lohela, M., Ikenberg, K., M\u00e4kinen, T., Korff, T., Saaristo, A., Jeltsch, M., Augustin, H. G., Alitalo, K. Intrinsic versus microenvironmental regulation of lymphatic endothelial cell phenotype and function.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    17, 2006\u20132013 (2003)\n                  <\/jats:p>","DOI":"10.1096\/fj.03-0179com","type":"journal-article","created":{"date-parts":[[2003,11,3]],"date-time":"2003-11-03T20:47:39Z","timestamp":1067892459000},"page":"2006-2013","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":65,"title":["Intrinsic versus microenvironmental regulation of lymphatic endothelial cell phenotype and function"],"prefix":"10.1096","volume":"17","author":[{"given":"Tanja","family":"Veikkola","sequence":"first","affiliation":[{"name":"Molecular\/Cancer Biology Laboratory Ludwig Institute for Cancer Research Biomedicum Helsinki Haartman Institute Helsinki University Central Hospital 00014 University of Helsinki  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Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas","family":"Korff","sequence":"additional","affiliation":[{"name":"Department of Vascular Biology and Angiogenesis Research Tumor Biology Center  D-79106 Freiburg Germany"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anne","family":"Saaristo","sequence":"additional","affiliation":[{"name":"Molecular\/Cancer Biology Laboratory Ludwig Institute for Cancer Research Biomedicum Helsinki Haartman Institute Helsinki University Central Hospital 00014 University of Helsinki  Finland"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Tatania","family":"Petrova","sequence":"additional","affiliation":[{"name":"Molecular\/Cancer Biology Laboratory Ludwig Institute for Cancer Research Biomedicum Helsinki Haartman Institute Helsinki University Central Hospital 00014 University of Helsinki  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