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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 adhesions in vitro.
- Source :
-
Cell biology international [Cell Biol Int] 2010 Apr 01; Vol. 34 (5), pp. 513-22. Date of Electronic Publication: 2010 Apr 01. - Publication Year :
- 2010
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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 :
- Animals
Apoptosis Regulatory Proteins
Cell Communication physiology
Cell Line, Tumor
Chemokines, CXC genetics
Focal Adhesion Protein-Tyrosine Kinases metabolism
GTP-Binding Proteins
Humans
Integrin alpha2beta1 metabolism
Intracellular Signaling Peptides and Proteins genetics
Intracellular Signaling Peptides and Proteins metabolism
Mice
Mice, Nude
Paxillin metabolism
Recombinant Fusion Proteins genetics
Recombinant Fusion Proteins metabolism
cdc42 GTP-Binding Protein metabolism
p21-Activated Kinases genetics
p21-Activated Kinases metabolism
rac1 GTP-Binding Protein metabolism
ral Guanine Nucleotide Exchange Factor genetics
ral Guanine Nucleotide Exchange Factor metabolism
rap1 GTP-Binding Proteins metabolism
Cell Adhesion physiology
Cell Movement physiology
Chemokines, CXC metabolism
Collagen Type I metabolism
Focal Adhesions metabolism
Focal Adhesions ultrastructure
Tongue Neoplasms metabolism
Tongue Neoplasms pathology
Subjects
Details
- Language :
- English
- ISSN :
- 1095-8355
- Volume :
- 34
- Issue :
- 5
- Database :
- MEDLINE
- Journal :
- Cell biology international
- Publication Type :
- Academic Journal
- Accession number :
- 20067447
- Full Text :
- https://doi.org/10.1042/CBI20090108