Laminin-derived peptide AG73 regulates migration, invasion, and protease activity of human oral squamous cell carcinoma cells through syndecan-1 and beta1 integrin.
Squamous cell carcinoma is a prevalent head and neck tumor with high mortality. We studied the role played by laminin alpha1 chain peptide AG73 on migration, invasion, and protease activity of cells (OSCC) from human oral squamous cell carcinoma. Immunohistochemistry and immunofluorescence analyzed expression of laminin alpha1 chain and MMP9 in oral squamous cells carcinoma in vivo and in vitro. Migratory activity of AG73-treated OSCC cells was investigated by monolayer wound assays and in chemotaxis chambers. AG73-induced invasion was assessed in Boyden chambers. Invasion depends on MMPs. Conditioned media from cells grown on AG73 was subjected to zymography. We searched for AG73 receptors related to these activities in OSCC cells. Immunofluorescence analyzed AG73-induced colocalization of syndecan-1 and beta1 integrin. Cells had these receptors silenced by siRNA, followed by treatment with AG73 and analysis of migration, invasion, and protease activity. Oral squamous cell carcinoma expresses laminin alpha1 chain and MMP9. OSCC cells treated with AG73 showed increased migration, invasion, and protease activity. AG73 induced colocalization of syndecan-1 and beta1 integrin. Knockdown of these receptors decreased AG73-dependent migration, invasion, and protease activity. Syndecan-1 and beta1 integrin signaling downstream of AG73 regulate migration, invasion, and MMP production by OSCC cells.
Siqueira
Adriane S
AS
Department of Cell and Developmental Biology, Institute of Biomedical Sciences, University of São Paulo, Av. Prof. Lineu Prestes,1524 Ed. Biomédicas 1, sala 302, São Paulo, SP, 05508-000, Brazil.
Gama-de-Souza
Letícia N
LN
Arnaud
Maria Vanda C
MV
Pinheiro
João J V
JJ
Jaeger
Ruy G
RG
D000328:Adult; D000368:Aged; D002294:Carcinoma, Squamous Cell / Q000473:pathology*; D045744:Cell Line, Tumor; D002465:Cell Movement; D005260:Female; D006801:Humans; D019012:Integrin beta1 / Q000378:metabolism*; D007797:Laminin / Q000032:analysis / Q000378:metabolism*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000378:metabolism*; D008875:Middle Aged; D009062:Mouth Neoplasms / Q000473:pathology*; D009361:Neoplasm Invasiveness; D053668:Syndecan-1 / Q000378:metabolism*
D019012:Integrin beta1; D007797:Laminin; C508241:SDC1 protein, human; D053668:Syndecan-1; C084098:laminin A; D020780:Matrix Metalloproteinase 9