LIGHT, a member of the TNF superfamily, induces morphological changes and delays proliferation in the human rhabdomyosarcoma cell line RD.
LIGHT is a member of the tumor necrosis factor (TNF) superfamily, which binds two known receptors, lymphotoxin-beta receptor (LTbetaR) and the herpesvirus entry mediator (HVEM)/TR2. We investigated the effects of LIGHT on the human rhabdmyosarcoma cell line RD. LIGHT delayed cell proliferation and induced morphological changes of the cells. These effects were not shown by other TNF family ligands such as TNFalpha and LTalpha, which induced the transcriptional activity of nuclear factor-kappaB (NF-kappaB) and NF-kappaB-responsible chemokine productions in the same manner as did LIGHT. LTalpha1beta2, another TNF family ligand for LTbetaR, was shown to have similar activities in RD cells as LIGHT. Both LIGHT and LTalpha1beta2 induced the expression of muscle-specific genes such as smooth muscle (SM) alpha-actin, while TNFalpha and LTalpha did not. These findings indicate that LIGHT may be a novel inducer of RD cell differentiation associated with SM alpha-actin expression through the LTbetaR.
Hikichi
Y
Y
Discovery Research Laboratories I, Pharmaceutical Research Division, Takeda Chemical Industries, Ltd., 10 Wadai, Tsukuba, Ibaraki 300-4293, Japan.
Matsui
H
H
Tsuji
I
I
Nishi
K
K
Yamada
T
T
Shintani
Y
Y
Onda
H
H
D000199:Actins / Q000096:biosynthesis / Q000235:genetics; D002455:Cell Division / Q000187:drug effects; D018946:Chemokine CCL5 / Q000096:biosynthesis; D005434:Flow Cytometry; D006801:Humans; D016209:Interleukin-8 / Q000096:biosynthesis; D007700:Kinetics; D008233:Lymphotoxin-alpha / Q000494:pharmacology; D008565:Membrane Proteins / Q000494:pharmacology*; D009124:Muscle Proteins / Q000096:biosynthesis / Q000235:genetics; D016328:NF-kappa B / Q000378:metabolism; D012334:RNA, Neoplasm / Q000096:biosynthesis; D012208:Rhabdomyosarcoma / Q000235:genetics / Q000378:metabolism / Q000473:pathology*; D014407:Tumor Cells, Cultured; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology*
D000199:Actins; D018946:Chemokine CCL5; D016209:Interleukin-8; D008233:Lymphotoxin-alpha; D008565:Membrane Proteins; D009124:Muscle Proteins; D016328:NF-kappa B; D012334:RNA, Neoplasm; C505914:TNFSF14 protein, human; D053326:Tumor Necrosis Factor Ligand Superfamily Member 14; D014409:Tumor Necrosis Factor-alpha