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Integrin beta4 signaling on mammary tumor cell adhesion to brain microvascular endothelium
Author(s) -
Fu Bingmei M,
Fan Jie,
Cai Bin,
Zeng Min,
Hao Yanyan,
Giancotti Filippo G
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.634.3
Integrin signaling contributes to tumor survival, progression and invasion. To investigate the role of β4 signaling in tumor adhesion, we measured the adhesion of mouse mammary carcinoma expressing either wild‐type (WT) or mutant β4 (1355T) to mouse brain microvascular endothelial cell (bEnd3) monolayers under normal and increased permeability by vascular endothelial growth factor (VEGF), and after pretreatment of tumor cells with antibodies blocking α6, α5, β1 integrins, or pretreatment of the bEnd3 with anti‐laminin‐5. Our results showed that in 60 min, there was no significant difference in the adhesion of WT and 1355T cells under normal and increased permeability conditions. About 80% or more of WT and 1355T cell adhesion occurred at the junctions of endothelial cells. 1nM VEGF significantly increased bEnd3 monolayer permeability to albumin, disrupted the inter‐endothelial junction proteins and enhanced the adhesion of both WT and 1355T, while anti‐integrin subunits and anti‐laminin‐5 reduced their adhesion. Immunostaining of hemidesmosomes, a junction complex formed by α6β4 and ECM laminin‐5, revealed no significant difference between WT and 1355T. Our results suggest that although β4 signaling promotes tumor cell survival and invasion, it does not alter tumor cell adhesion, possibly by not interfering with the hemidesmosomes formation. Supported by NIH U54CA137788‐01 and SC1CA153325‐01A1.