Cytoplasmic and/or nuclear staining of beta-catenin is associated with lung metastasis.
Beta-catenin is involved in cell motility in the extracellular matrix, and is expressed in normal and neoplastic mesenchymal cells. In order to clarify whether beta-catenin expression in the cytoplasm and/or nucleus is associated with a propensity for pulmonary metastasis in osteosarcoma, the LM8 murine osteosarcoma cell line with a high metastatic potential to the lung was compared with original Dunn cells in terms of the beta-catenin expression level. Both osteosarcoma cell lines lost membrane localization of beta-catenin. However, beta-catenin gene had no mutation in exon 3 by direct sequence analysis. A large number of LM8 cells showed diffuse cytoplasmic and/or nuclear staining of beta-catenin (30.8 per high power field (HPF)), while a much smaller number of Dunn cells showed expression of beta-catenin (7.7 per HPF). Cells with positive staining of beta-catenin were frequently seen at the invasive front and in intravenous tumor deposits within the metastatic lesions to the lung. Thus, LM8 cells express a larger amount of the beta-catenin protein than Dunn cells, as judged by immunoblot analysis. In five resected cases of pulmonary metastasis, translocation of beta-catenin to the cytoplasm and/or nucleus of osteosarcoma cells was detected, although seven primary osteosarcomas cells that did not metastasize for more than five years did not show beta-catenin expression. These data indicate that the cytoplasmic and/or nuclear staining of beta-catenin is a biological marker of metastatic potential of osteosarcoma to the lung.
Department of Pathology, Tokyo Medical University, Tokyo, Japan.
Keiichi
K
Iwaya
Hitoshi
H
Ogawa
Masahiko
M
Kuroda
Miki
M
Izumi
Tsuyoshi
T
Ishida
Kiyoshi
K
Mukai
D000818:Animals; D001483:Base Sequence; D014408:Biomarkers, Tumor / Q000032:analysis; D001859:Bone Neoplasms / Q000473:pathology; D002467:Cell Nucleus / Q000473:pathology*; D003593:Cytoplasm / Q000473:pathology*; D003598:Cytoskeletal Proteins / Q000032:analysis* / Q000235:genetics; D017931:DNA Primers; D006801:Humans; D008175:Lung Neoplasms / Q000473:pathology* / Q000556:secondary*; D008297:Male; D051379:Mice; D008809:Mice, Inbred C3H; D012516:Osteosarcoma; D016133:Polymerase Chain Reaction; D012878:Skin Neoplasms / Q000473:pathology; D015534:Trans-Activators / Q000032:analysis* / Q000235:genetics; D014407:Tumor Cells, Cultured; D051176:beta Catenin
D014408:Biomarkers, Tumor; C495270:CTNNB1 protein, human; C495267:CTNNB1 protein, mouse; D003598:Cytoskeletal Proteins; D017931:DNA Primers; D015534:Trans-Activators; D051176:beta Catenin