VEGFR-2 expression in carcinoid cancer cells and its role in tumor growth and metastasis.
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.
Silva
Scott R
SR
Department of Surgery, The University of Texas Medical Branch, Galveston, TX, USA.
Bowen
Kanika A
KA
Rychahou
Piotr G
PG
Jackson
Lindsey N
LN
Weiss
Heidi L
HL
Lee
Eun Y
EY
Townsend
Courtney M
CM
Evers
B Mark
BM
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*
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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