RRC ID 71721
Author Nagai M, Kyakumoto S, Sato N.
Title Cancer cells responsible for humoral hypercalcemia express mRNA encoding a secreted form of ODF/TRANCE that induces osteoclast formation.
Journal Biochem Biophys Res Commun
Abstract A novel cDNA encoding a secreted form of osteoclast differentiation factor/tumor necrosis factor-related activation-induced cytokine (sODF/TRANCE, GenBank Accession No. AB037599) was sequenced from 5' RACE cDNA clones of squamous cell carcinoma cell lines, SCC-4 and T3M-1 Cl.2, of which parental malignant tissues had caused severe humoral hypercalcemia. The sODF/TRANCE cDNA was composed of unknown 5' end sequence followed by the 100% identical sequence of the ODF/TRANCE extracellular domain-coding region. The longest open reading frame (ORF) of the novel cDNA completely matched the 3' end of the ORF of the ODF/TRANCE cDNA encoding C-terminal amino acid residues (74-318) in the extracellular region. The corresponding protein that reacted with the antibody specific for the extracellular domain of ODF/TRANCE was detected in the culture media conditioned by the cancer cells. Furthermore, human promyeloblastic leukemia cells, HL60, differentiated into osteoclast-like cells (OCLs) when cultured in the media conditioned by SCC-4 and T3M-1 Cl. 2 cells. The differentiation of HL60 cells into OCLs was inhibited by the anti-ODF/TRANCE antibody. These results strongly suggest that sODF/TRANCE plays an important role in enhanced bone-resorption in humoral hypercalcemia of malignancy.
Volume 269(2)
Pages 532-6
Published 2000-3-16
DOI 10.1006/bbrc.2000.2314
PII S0006-291X(00)92314-3
PMID 10708588
MeSH Amino Acid Sequence Base Sequence Carrier Proteins / genetics* Cells, Cultured DNA, Complementary Humans Hypercalcemia / etiology* Immunohistochemistry Membrane Glycoproteins / genetics* Molecular Sequence Data Neoplasms / complications* Osteoclasts / cytology* RANK Ligand RNA, Messenger / genetics* Receptor Activator of Nuclear Factor-kappa B Tumor Cells, Cultured Tumor Necrosis Factor-alpha / genetics
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Human and Animal Cells T3M-1 Clone2(RCB1015) HFL-I(RCB0521) HL60(RCB0041)