Transforming growth factor-beta1 stimulates contraction of human glioblastoma cell-mediated collagen lattice through enhanced alpha2 integrin expression.
Rapid invasiveness is a feature of the highly malignant glioblastoma tumor and is closely related to patient prognosis. The interaction between extracellular matrix (ECM) and cell surface receptors such as integrin heterodimers play a key role in the process of tumor invasion. We investigated the effects of transforming growth factor-beta1 (TGF-beta1), which is a mitogenic factor for glial cells, on integrin expression in T98G human glioblastoma cells using an in vitro model 3-dimensional collagen lattice. Exogenously applied TGF-beta1 dose-dependently enhanced collagen lattice contraction. Among the inhibitory antibodies tested against alpha integrin subunits, the anti-alpha2 antibody, P1-E6, alone prevented the enhanced contractile response by TGF-beta1, whereas any alpha integrin antibody (including P1-E6) had little effect on lattice contraction when cultured without TGF-beta1. RT-PCR analysis revealed that TGF-beta1 strongly increased alpha2 integrin transcript level. Furthermore, pretreatment with antisense phosphorothioate oligodeoxynucleotides against human alpha2 integrin using hemagglutinating virus of Japan (HVJ) liposome-mediated transfer prevented the effects of TGF-beta1 and also reduced the lattice contraction even in the absence of TGF-beta1. This data indicates that increased expression of alpha2 integrin is responsive to enhanced collagen lattice contraction by TGF-beta1. We suggest that TGF-beta1 exerts its effects on the invasive property of glioblastoma cells via upregulation of the alpha2 integrin subunit expression.
Miyake
K
K
Department of Neurological Surgery, Kagawa Medical University, Japan.
Kimura
S
S
Nakanishi
M
M
Hisada
A
A
Hasegawa
M
M
Nagao
S
S
Abe
Y
Y
D015703:Antigens, CD / Q000235:genetics*; D003094:Collagen / Q000378:metabolism*; D004305:Dose-Response Relationship, Drug; D005109:Extracellular Matrix / Q000737:chemistry / Q000378:metabolism; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects; D018014:Gene Transfer Techniques; D005909:Glioblastoma; D006801:Humans; D039421:Integrin alpha2; D039422:Integrin alpha3; D016023:Integrins / Q000235:genetics; D008081:Liposomes; D016376:Oligonucleotides, Antisense / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D018108:Respirovirus; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic / Q000187:drug effects; D016212:Transforming Growth Factor beta / Q000494:pharmacology*; D014407:Tumor Cells, Cultured / Q000378:metabolism / Q000473:pathology
D015703:Antigens, CD; D039421:Integrin alpha2; D039422:Integrin alpha3; D016023:Integrins; D008081:Liposomes; D016376:Oligonucleotides, Antisense; D012333:RNA, Messenger; D016212:Transforming Growth Factor beta; D003094:Collagen