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VEGFR‐2 expression in carcinoid cancer cells and its role in tumor growth and metastasis
Author(s) -
Silva Scott R.,
Bowen Kanika A.,
Rychahou Piotr G.,
Jackson Lindsey N.,
Weiss Heidi L.,
Lee Eun Y.,
Townsend Courtney M.,
Evers B. Mark
Publication year - 2010
Publication title -
international journal of cancer
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.475
H-Index - 234
eISSN - 1097-0215
pISSN - 0020-7136
DOI - 10.1002/ijc.25441
Subject(s) - angiogenesis , metastasis , cancer research , pi3k/akt/mtor pathway , biology , cell growth , cell culture , carcinoid tumors , protein kinase b , signal transduction , pathology , cancer , microbiology and biotechnology , medicine , genetics
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.