Tumour necrosis factor-alpha provokes upregulation of alpha2beta1 and alpha5beta1 integrins, and cell migration in OST osteosarcoma cells.
OST cells enhance the induction of matrix metalloproteinase (MMP)-9 by tumour necrosis factor (TNF)-alpha and the corresponding metastasis to lungs in vivo (Kawashima et al., 1994). We focused on the adhesive and migratory properties of OST cells, and investigated the expression of integrins in OST cells stimulated by TNFalpha in vitro. OST cells potentiated not only adhesion to the extracellular matrix (ECM) but also the migration on ECM. On competitive reverse transcription-polymerase chain reaction (RT-PCR) analyses, the amounts of alpha2 (4.9-fold), alpha5 (1.2-fold) and alpha(v) (4.9-fold) were upregulated by TNFalpha at the transcriptional level. Alpha-5 showed a slight increase by flow cytometry; however, alpha2 and alphav integrins remained unchanged at the protein level. Immunofluorescence study disclosed integrins of alpha2beta1 and alpha5beta1 were much clustered at cell processes by TNFalpha stimulation, probably related to increased cell adhesion and migration. Therefore, the upregulation of alpha2beta1 and alpha5beta1 integrins seems to contribute to tumour invasion and metastatic potential.
Kawashima
A
A
Department of Pathology (I), School of Medicine, Kanazawa University, Kanazawa, Japan. kawasima@med.kanazawa-u.ac.jp
Kawahara
E
E
Tokuda
R
R
Nakanishi
I
I
D002448:Cell Adhesion / Q000502:physiology; D002460:Cell Line / Q000166:cytology / Q000378:metabolism; D002465:Cell Movement / Q000187:drug effects / Q000502:physiology; D005109:Extracellular Matrix / Q000502:physiology; D005434:Flow Cytometry; D006801:Humans; D016023:Integrins / Q000096:biosynthesis* / Q000187:drug effects; D008856:Microscopy, Fluorescence; D012516:Osteosarcoma / Q000378:metabolism*; D038981:Receptors, Collagen; D017469:Receptors, Fibronectin / Q000096:biosynthesis* / Q000187:drug effects; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism* / Q000494:pharmacology; D015854:Up-Regulation / Q000187:drug effects / Q000502:physiology
D016023:Integrins; D038981:Receptors, Collagen; D017469:Receptors, Fibronectin; D014409:Tumor Necrosis Factor-alpha