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Expression of tumour-suppressing chemokine BRAK/CXCL14 reduces cell migration rate of HSC-3 tongue carcinoma cells and stimulates attachment to collagen and formation of elongated focal adhesionsin vitro
- Source :
- Cell Biology International. 34:513-522
- Publication Year :
- 2010
- Publisher :
- Wiley, 2010.
-
Abstract
- BRAK/CXCL14 (breast- and kidney-expressed chemokine/CXC chemokine ligand 14) is a chemokine that is expressed in many normal cells and tissues but is absent from or expressed at very low levels in transformed cells and cancerous tissues, including HNSCC (head and neck squamous cell carcinoma). We reported previously that the forced expression of BRAK/CXCL14 in HNSCC (HSC-3 BRAK) cells decreased the rate of tumour formation and size of tumour xenografts compared with mock-vector-introduced (HSC-3 Mock) cells in athymic nude mice, even though the growth rates of these cells were the same under in vitro culture conditions, suggesting that high-level expression of the gene is important for the suppression of tumour establishment in vivo. For the first step to study the mechanisms of BRAK-dependent tumour suppression, we compared characteristics between HSC-3 BRAK and HSC-3 Mock cells under in vitro culture conditions. The cell migration rate was lower in HSC-3 BRAK cells than in HSC-3 Mock cells. Also, HSC-3 BRAK cells showed more rapid adhesion than HSC-3 Mock cells when cultured on type I collagen-coated dishes but not on fibronectin or laminin 1-coated ones. This adhesion was mediated by alpha2beta1 integrin. Immunofluorescent analysis of the cells cultured on type I collagen showed that HSC-3 BRAK cells formed much more elongated focal adhesions co-localized with paxillin and actin stress fibres than did HSC-3 Mock cells. Treatment of parental HSC-3 cells with recombinant BRAK stimulated the activation of Rap1, which is a ras family small GTPase, and formation of elongated focal adhesions, indicating that the difference in cell character observed between HSC-3 Mock and HSC-3 BRAK was not due to selection of clones of different character but due to expression of BRAK in the cells. The characteristic morphology of focal adhesions in HSC-3 BRAK cells was perturbed by the introduction of an expression vector of the Rap-binding domain of the Ral guanine nucleotide dissociation stimulator, a target of Rap1, into HSC-3 BRAK cells, suggesting that Rap1 regulated the formation of the morphology of the focal adhesions. These data indicate that the expression of BRAK stimulated the formation of elongated focal adhesions of the HSC-3 cells in an autocrine or paracrine fashion, in which stimulation may be responsible for the reduced migration of the cells.
- Subjects :
- rac1 GTP-Binding Protein
Recombinant Fusion Proteins
Mice, Nude
Cell Communication
Biology
Collagen Type I
Focal adhesion
Mice
Paracrine signalling
Cell Movement
GTP-Binding Proteins
Cell Line, Tumor
ral Guanine Nucleotide Exchange Factor
Cell Adhesion
Animals
Humans
Ral Guanine Nucleotide Exchange Factor
cdc42 GTP-Binding Protein
Cell adhesion
CXCL14
Paxillin
Focal Adhesions
Intracellular Signaling Peptides and Proteins
rap1 GTP-Binding Proteins
Cell migration
Cell Biology
General Medicine
Tongue Neoplasms
Cell biology
p21-Activated Kinases
Cell culture
Focal Adhesion Protein-Tyrosine Kinases
biology.protein
Integrin alpha2beta1
Apoptosis Regulatory Proteins
Chemokines, CXC
Subjects
Details
- ISSN :
- 10958355 and 10656995
- Volume :
- 34
- Database :
- OpenAIRE
- Journal :
- Cell Biology International
- Accession number :
- edsair.doi.dedup.....e8a44e3ddb3f20b682e7fe9d36b22a74