Patched haploinsufficient mouse rhabdomyosarcoma overexpress secreted phosphoprotein 1 and matrix metalloproteinases

Eur J Cancer. 2007 May;43(8):1308-17. doi: 10.1016/j.ejca.2007.02.008. Epub 2007 Apr 30.


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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Blotting, Western
  • DNA, Complementary / metabolism
  • Enzyme-Linked Immunosorbent Assay
  • Gene Expression
  • Heterozygote
  • Humans
  • Immunohistochemistry
  • Matrix Metalloproteinases / genetics
  • Matrix Metalloproteinases / metabolism*
  • Mice
  • Microarray Analysis
  • Mutation / genetics
  • Neoplasm Proteins / genetics
  • Neoplasm Proteins / metabolism*
  • Osteopontin / genetics
  • Osteopontin / metabolism*
  • RNA, Neoplasm / metabolism
  • Reverse Transcriptase Polymerase Chain Reaction
  • Rhabdomyosarcoma / genetics
  • Rhabdomyosarcoma / metabolism*


  • DNA, Complementary
  • Neoplasm Proteins
  • RNA, Neoplasm
  • Osteopontin
  • Matrix Metalloproteinases