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.

Whole-exome characterization of pancreatic neuroendocrine tumor cell lines BON-1 and QGP-1

“…A high-molecular-weight band was visible on DNA gel electrophoresis, excluding DNA degradation. Short tandem repeat profiling using a Powerplex Kit (Promega) of BON-1 and QGP-1 gave results consistent with those obtained by the original group (Silva et al 2011) and the JRCB database, respectively, thus confirming the cell lines' identity.…”

Tumor VEGF:VEGFR2 autocrine feed-forward loop triggers angiogenesis in lung cancer

“…This change from prevascular hyperplasia to highly vascularized tumors has been referred to as the angiogenic switch (1). In recent years, several studies have reported expression of VEGFR1 as well as VEGFR2 on tumor cells (3)(4)(5). An intriguing finding related to tumor cell expression of Flt1 was the observation that VEGF secreted by tumor cells triggers tumor cell proliferation by binding Flt1 (6).…”

Role of targeted agents in neuroendocrine tumors: Results from a meta-analysis

“…26,28 Moreover the VEGF receptor-2 (VEGFR-2) is also generally over-expressed also in gastro-intestinal carcinoid tumors and carcinoid cancers. 26,29 Thus, targeting these markers potentially arrest the NETs related-angiogenesis inducing, as a consequence, a tumor downstage and an improvement in PFS/ OS. 12,20,21 The present study is a systematic review and a meta-analysis of trials to assess the efficacy of targeted agents in patients with advanced NET.…”