title: Circulating lymphangiogenic growth factors in gastrointestinal solid tumors, could they be of any clinical significance?
abstract: Metastasis is the principal cause of cancer mortality, with the lymphatic system being the first route of tumor dissemination. The glycoproteins VEGF-C and VEGF-D are members of the vascular endothelial growth factor (VEGF) family, whose role has been recently recognized as lymphatic system regulators during embryogenesis and in pathological processes such as inflammation, lymphatic system disorders and malignant tumor metastasis. They are ligands for the VEGFR-3 receptor on the membrane of the lymphatic endothelial cell, resulting in dilatation of existing lymphatic vessels as well as in vegetation of new ones (lymphangiogenesis). Their determination is feasible in the circulating blood by immunoabsorption and in the tissue specimen by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Experimental and clinicopathological studies have linked the VEGF-C, VEGF-D/VEGFR3 axis to lymphatic spread as well as to the clinical outcome in several human solid tumors. The majority of these data are derived from surgical specimens and malignant cell series, rendering their clinical application questionable, due to subjectivity factors and post-treatment quantification. In an effort to overcome these drawbacks, an alternative method of immunodetection of the circulating levels of these molecules has been used in studies on gastric, esophageal and colorectal cancer. Their results denote that quantification of VEGF-C and VEGF-D in blood samples could serve as lymph node metastasis predictive biomarkers and contribute to preoperative staging of gastrointestinal malignancies.
authors.affiliation: Third Department of Surgery, General Hospital of Athens G.Gennimatas Psaron 20 str. Agia Paraskevi, Athens, Greece. theotsir@med.uoa.gr
authors.forename: Theodore D
authors.initials: TD
authors.lastname: Tsirlis
authors.forename: George
authors.initials: G
authors.lastname: Papastratis
authors.forename: Kyriaki
authors.initials: K
authors.lastname: Masselou
authors.forename: Christos
authors.initials: C
authors.lastname: Tsigris
authors.forename: Antonis
authors.initials: A
authors.lastname: Papachristodoulou
authors.forename: Alkiviadis
authors.initials: A
authors.lastname: Kostakis
authors.forename: Nikolaos I
authors.initials: NI
authors.lastname: Nikiteas
mesh_terms: D014408:Biomarkers, Tumor / Q000097:blood*; D015179:Colorectal Neoplasms / Q000378:metabolism / Q000503:physiopathology; D004938:Esophageal Neoplasms / Q000378:metabolism / Q000503:physiopathology; D005770:Gastrointestinal Neoplasms / Q000378:metabolism* / Q000473:pathology / Q000503:physiopathology; D006801:Humans; D042583:Lymphangiogenesis; D008207:Lymphatic Metastasis; D008208:Lymphatic System / Q000378:metabolism* / Q000503:physiopathology; D009367:Neoplasm Staging; D011237:Predictive Value of Tests; D011379:Prognosis; D013274:Stomach Neoplasms / Q000378:metabolism / Q000503:physiopathology; D042582:Vascular Endothelial Growth Factor C / Q000097:blood*; D042643:Vascular Endothelial Growth Factor D / Q000097:blood*; D040321:Vascular Endothelial Growth Factor Receptor-3 / Q000378:metabolism
chemical_list: D014408:Biomarkers, Tumor; D042582:Vascular Endothelial Growth Factor C; D042643:Vascular Endothelial Growth Factor D; D040321:Vascular Endothelial Growth Factor Receptor-3