Autocrine TGF-beta-regulated expression of adhesion receptors and integrin-linked kinase in HT-144 melanoma cells correlates with their metastatic phenotype.
We have previously shown that 2 human melanoma cell lines, the metastatic HT-144 and the non-metastatic SK-Mel-2 cells, exhibit marked in vitro heterogeneity with respect to integrin expression, migration and invasion potential. Here, we provide evidence that HT-144 melanoma cells, but not SK-Mel-2 cells, undergo a reversible transition to a fibroblastoid morphology following treatment with either their own serum-free acidified conditioned medium or biologically active exogenous TGF-beta1, thus identifying TGF-beta as an autocrine regulator of the spindle shape morphology of HT-144 melanoma cells. The fibroblastoid phenotype correlated with up-regulated beta1 and beta3 integrin and down-regulated E-cadherin expression, as shown by flow cytometry, Western blot and RT-PCR, as well as up-regulated expression of the matrix metalloproteinase MMP-9, as demonstrated by zymography. Our data further illustrate the TGF-beta1-dependent up-regulation of integrin-linked kinase and the nuclear translocation of beta-catenin, 2 intracellular proteins involved in integrin and cadherin signaling.
Janji
B
B
Laboratoire Franco-Luxembourgeois de Recherche Biomédicale (CNRS/CRP-Santé), University Center, Luxembourg.
Melchior
C
C
Gouon
V
V
Vallar
L
L
Kieffer
N
N
D015703:Antigens, CD / Q000096:biosynthesis*; D015153:Blotting, Western; D015820:Cadherins / Q000096:biosynthesis*; D002465:Cell Movement; D048429:Cell Size / Q000187:drug effects; D017364:Collagenases / Q000096:biosynthesis / Q000378:metabolism; D015536:Down-Regulation; D005434:Flow Cytometry; D006801:Humans; D019012:Integrin beta1 / Q000096:biosynthesis*; D039661:Integrin beta3; D020780:Matrix Metalloproteinase 9; D008545:Melanoma / Q000201:enzymology / Q000378:metabolism* / Q000473:pathology / Q000556:secondary*; D010641:Phenotype; D010980:Platelet Membrane Glycoproteins / Q000096:biosynthesis*; D017346:Protein Serine-Threonine Kinases / Q000096:biosynthesis*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured; D015854:Up-Regulation; D000099200:Scaffold Protein ILK
D015703:Antigens, CD; D015820:Cadherins; D017364:Collagenases; D019012:Integrin beta1; D039661:Integrin beta3; D020780:Matrix Metalloproteinase 9; D010980:Platelet Membrane Glycoproteins; D017346:Protein Serine-Threonine Kinases; D016212:Transforming Growth Factor beta; D000099200:Scaffold Protein ILK