Semaphorin SEMA3F has a repulsing activity on breast cancer cells and inhibits E-cadherin-mediated cell adhesion.
Previously, we demonstrated that loss of SEMA3F, a secreted semaphorin encoded in 3p21.3, is associated with higher stages in lung cancer and primary tumor cells studied with anti-vascular endothelial growth factor (VEGF) and SEMA3F antibodies. In vitro, SEMA3F inhibits cell spreading; this activity is opposed by VEGF. These results suggest that VEGF and SEMA3F compete for binding to their common neuropilin receptor. In the present report, we investigated the attractive/repulsive effects of SEMA3F on cell migration when cells were grown in a three-dimensional system and exposed to a SEMA3F gradient. In addition, we adapted the neurobiologic stripe assay to analyze the migration of tumor cells in response to SEMA3F. In the motile breast cancer cell line C100, which expresses both neuropilin-1 (NRP1) and neuropilin-2 (NRP2) receptors, SEMA3F had a repulsive effect, which was blocked by anti-NRP2 antibody. In less motile MCF7 cells, which express only NRP1, SEMA3F inhibited cell contacts with loss of membrane-associated E-cadherin and beta-catenin without motility induction. Cell spreading and proliferation were reduced. These results support the concept that in a first step during tumorigenesis, normal tissues expressing SEMA3F would try to prevent tumor cells from spreading and attaching to the stroma for further implantation.
Nasarre
Patrick
P
IPBC, CNRS UMR 6187, Université de Poitiers, 40 Avenue du Recteur Pineau, Poitiers Cedex 86022, France.
Kusy
Sophie
S
Constantin
Bruno
B
Castellani
Valérie
V
Drabkin
Harry A
HA
Bagnard
Dominique
D
Roche
Joëlle
J
D001943:Breast Neoplasms / Q000378:metabolism / Q000473:pathology*; D015820:Cadherins / Q000737:chemistry* / Q000378:metabolism; D002448:Cell Adhesion; D002462:Cell Membrane / Q000378:metabolism; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D003598:Cytoskeletal Proteins / Q000378:metabolism; D005260:Female; D006801:Humans; D007668:Kidney / Q000378:metabolism; D008565:Membrane Proteins / Q000378:metabolism*; D009419:Nerve Tissue Proteins / Q000378:metabolism*; D039942:Neuropilin-1 / Q000235:genetics / Q000378:metabolism; D039943:Neuropilin-2 / Q000235:genetics / Q000378:metabolism; D015534:Trans-Activators / Q000378:metabolism; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism; D051176:beta Catenin
C495270:CTNNB1 protein, human; D015820:Cadherins; D003598:Cytoskeletal Proteins; D008565:Membrane Proteins; D009419:Nerve Tissue Proteins; D039943:Neuropilin-2; C491230:SEMA3F protein, human; D015534:Trans-Activators; D042461:Vascular Endothelial Growth Factor A; D051176:beta Catenin; D039942:Neuropilin-1