Expression of collagenase-3 (MMP-13) in c-Fos-induced osteosarcomas and chondrosarcomas is restricted to a subset of cells of the osteo-/chondrogenic lineage

• Published in: Differentiation (London) Vol. 69; no. 1; pp. 49 - 57
• Main Authors: Tuckermann, Jan Peter, Vallon, Rüdiger, Gack, Sabine, Grigoriadis, Agamemnon E., Porte, Dominique, Lutz, Arne, Wagner, Erwin F., Schmidt, Jörg, Angel, Peter
• Format: Journal Article
• Language: English
• Published: Berlin/Wien Elsevier B.V 01.12.2001; Blackwell Wissenschafts‐Verlag; Blackwell
• Subjects: Animals; AP-1/c-Fos; Biological and medical sciences; cbfa-1; Cbfa1 gene; Cell Differentiation; Cell differentiation, maturation, development, hematopoiesis; Cell Lineage; Cell physiology; chondrosarcoma; Chondrosarcoma - enzymology; Chondrosarcoma - etiology; Chondrosarcoma - pathology; collagenase 3; collagenase-3/MMP-13; Collagenases - genetics; Fundamental and applied biological sciences. Psychology; Genes, jun; hypertrophic chondrocyte; Immunohistochemistry; In Situ Hybridization; Matrix Metalloproteinase 13; Mice; Mice, Transgenic; Molecular and cellular biology; osteoblast; osteosarcoma; Osteosarcoma - enzymology; Osteosarcoma - etiology; Osteosarcoma - pathology; Proto-Oncogene Proteins c-fos - genetics; Proto-Oncogene Proteins c-fos - physiology; RNA, Messenger - genetics; chondrosarcoma; collagenase-3/MMP-13; cbfa-1; osteoblast; osteosarcoma; AP-1/c-Fos; hypertrophic chondrocyte; Chondrogenesis
• ISSN: 0301-4681; 1432-0436
• DOI: 10.1046/j.1432-0436.2001.690105.x

The interstitial collagenases have been suggested to play a critical role in bone formation, remodeling, and cancerogenesis. We have previously shown that during mouse development expression of collagenase-3 (MMP-13) is restricted to bone and cartilage (Gack et al., 1995; Tuckermann et al., 2000) and is affected in mice with altered c-Fos and Cbfa-1 expression (Gack et al., 1994; Porte et al., 1999). In this study, using immunohistochemistry (IHC) and in situ hybridization (ISH) techniques, we have identified cells of the osteoblastic lineage to be the origin of strongly enhanced levels of MMP-13 transcripts in c-fos-induced osteosarcomas. Expression in these cells is further increased in c-fos/c-jun double transgenic mice and paralleled by Cbfa-1 expression. Similarly, in spontaneous and radiation-induced osteosarcomas, both c-Fos and MMP-13 proteins are detectable, suggesting that overexpression of both genes is a characteristic feature of osteosarcomas of different origin. We also observed high levels of MMP-13 in c-Fos-induced chondrosarcomas. In osteoblast-like cells and in cells of late chondrocyte differentiation such as hypertrophic chondrocytes, high levels of MMP-13 transcripts were found. In contrast, in anaplastic areas of the tumors representing highly proliferating chondrocytes, no MMP-13 expression is detectable, suggesting that in addition to Fos/AP-1, bone-specific transcription factors are responsible for restricted expression of collagenase-3/MMP-13 in a specific subset of cells of bone and cartilage in physiology and pathology.