| First Author | De Bortoli M | Year | 2007 |
| Journal | Eur J Cancer | Volume | 43 |
| Issue | 8 | Pages | 1308-17 |
| PubMed ID | 17467979 | Mgi Jnum | J:121824 |
| Mgi Id | MGI:3712374 | Doi | 10.1016/j.ejca.2007.02.008 |
| Citation | De Bortoli M, et al. (2007) Patched haploinsufficient mouse rhabdomyosarcoma overexpress secreted phosphoprotein 1 and matrix metalloproteinases. Eur J Cancer 43(8):1308-1317 |
| abstractText | Rhabdomyosarcoma is the most common soft tissue sarcoma of childhood. Improving the management of rhabdomyosarcoma requires a better understanding of growth regulation. Patched haploinsufficient (Ptch+/-) mice spontaneously develop soft tissue sarcomas that resemble human rhabdomyosarcomas. Using microarray profiling and quantitative real-time reverse transcriptase polymerase chain reaction, we identified candidate genes differentially expressed in Ptch+/- mouse rhabdomyosarcoma relative to mature muscle. Overexpressed genes include Secreted Phosphoprotein 1 (Spp1, Osteopontin), and Matrix Metalloproteinases-2 and -14 (Mmp2 and Mmp14). Spp1 is an integrin-binding phosphoglycoprotein upregulated in carcinomas, and Mmps regulate tumour invasion. Immunochemical analyses of murine and human rhabdomyosarcoma specimens confirmed increased expression of Spp1, Mmp2, Mmp14, nuclear factor-kappa B (NF-kappaB) p65 and its phosphorylated active isoform. Neutralising Spp1 antibody decreased Mmp14 RNA in murine rhabdomyosarcoma cultures, indicating a positive regulatory role for extracellular Spp1. Plasma from rhabdomyosarcoma patients display elevated levels of SPP1. These results implicate Spp1, NF-kappaB, and Mmp activation as a putative signalling pathway involved in rhabdomyosarcoma growth. |
