title: VEGFR-2 expression in carcinoid cancer cells and its role in tumor growth and metastasis.
abstract: Carcinoid tumors are slow growing and highly vascular neuroendocrine neoplasms that are increasing in incidence. Previously, we showed that carcinoid tumors express vascular endothelial growth factor receptor 2 (VEGFR-2) in the epithelial compartment of carcinoid tumor sections; yet, its role is not completely understood. The purpose of our study was to: (i) assess the expression of VEGFR-2 in the novel human carcinoid cell line BON, (ii) to determine the role of PI3K/Akt signaling on VEGFR-2 expression and (iii) to assess the effect of VEGFR-2 on BON cell invasion, migration and proliferation. We found that, although VEGFR-2 is expressed in BON cells, reduction in VEGFR-2 expression actually enhanced proliferation, invasion, and migration of the BON cell line. Also, expression of VEGFR-2 was inversely related to PI3K signaling. Carcinoid liver metastases in mice demonstrated decreased VEGFR-2 expression. Furthermore, the expression of a truncated, soluble form of VEGFR-2 (sVEGFR-2), a protein demonstrated to inhibit cell growth, was detected in BON cells. The presence of VEGFR-2 in the epithelial component of carcinoid tumors and in the BON cell line suggests an alternate role for VEGFR-2, in addition to its well-defined role in angiogenesis. The expression of sVEGFR-2 may explain the inverse relationship between VEGFR-2 expression and PI3K/Akt signaling and the inhibitory effect VEGFR-2 has on BON cell proliferation, migration and invasion.
authors.affiliation: Department of Surgery, The University of Texas Medical Branch, Galveston, TX, USA.
authors.forename: Scott R
authors.initials: SR
authors.lastname: Silva
authors.forename: Kanika A
authors.initials: KA
authors.lastname: Bowen
authors.forename: Piotr G
authors.initials: PG
authors.lastname: Rychahou
authors.forename: Lindsey N
authors.initials: LN
authors.lastname: Jackson
authors.forename: Heidi L
authors.initials: HL
authors.lastname: Weiss
authors.forename: Eun Y
authors.initials: EY
authors.lastname: Lee
authors.forename: Courtney M
authors.initials: CM
authors.lastname: Townsend
authors.forename: B Mark
authors.initials: BM
authors.lastname: Evers
mesh_terms: D000818:Animals; D001483:Base Sequence; D002276:Carcinoid Tumor / Q000378:metabolism* / Q000473:pathology; D045744:Cell Line, Tumor; D049109:Cell Proliferation; D017931:DNA Primers; D004797:Enzyme-Linked Immunosorbent Assay; D006801:Humans; D007150:Immunohistochemistry; D008297:Male; D051379:Mice; D008819:Mice, Nude; D009362:Neoplasm Metastasis; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D015398:Signal Transduction; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000378:metabolism*
chemical_list: D017931:DNA Primers; D042461:Vascular Endothelial Growth Factor A; D019869:Phosphatidylinositol 3-Kinases; D040301:Vascular Endothelial Growth Factor Receptor-2; D051057:Proto-Oncogene Proteins c-akt
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