VEGFR‐2 expression in carcinoid cancer cells and its role in tumor growth and metastasis

• Published in: International journal of cancer 2011-03, Vol.128 (5), p.1045-1056
• Main Authors: Silva, Scott R., Bowen, Kanika A., Rychahou, Piotr G., Jackson, Lindsey N., Weiss, Heidi L., Lee, Eun Y., Townsend, Courtney M., Evers, B. Mark
• Format: Article
• Language: English
• Subjects: 1-Phosphatidylinositol 3-kinase; AKT protein; Angiogenesis; angiogenic factors and receptors; Animals; Base Sequence; Biological and medical sciences; Cancer; Carcinoid Tumor - metabolism; Carcinoid Tumor - pathology; Cell growth; Cell Line, Tumor; Cell migration; cell motility and migration; Cell Proliferation; DNA Primers; Enzyme-Linked Immunosorbent Assay; Humans; Immunohistochemistry; Kinases; Male; Medical research; Medical sciences; Metastases; Mice; Mice, Nude; Neoplasia; Neoplasm Metastasis; Neuroendocrine tumors; Phosphatidylinositol 3-Kinases - metabolism; Proto-Oncogene Proteins c-akt - metabolism; Reverse Transcriptase Polymerase Chain Reaction; Signal Transduction; tumor markers and detection of metastasis; Tumors; Vascular endothelial growth factor; Vascular Endothelial Growth Factor A - metabolism; Vascular endothelial growth factor receptor 2; Vascular Endothelial Growth Factor Receptor-2 - metabolism; Vascular endothelial growth factor receptors
• ISSN: 0020-7136; 1097-0215
• DOI: 10.1002/ijc.25441

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.