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Differential susceptibility of osteosarcoma cells and primary osteoblasts to cell detachment caused by snake venom metalloproteinase protein.

Abstract
The interaction of extracellular matrix with cells plays a key role in the regulation of cell adhesion, migration, proliferation as well as differentiation. Transformed cells express a different profile of adhesion molecules, which may mediate metastasis under specific matrix microenvironment. We here found that ROS 17/2.8 osteosarcoma cells and osteoblasts have different expression of alpha5 integrin, executing different fibronectin fibrillogenesis. As compared with ROS 17/2.8 cells, osteoblasts have higher expression of fibronectin, collagen, alpha5, beta1, alpha2 integrins and focal adhesion kinase as examined by immunostaining and flow cytometry. Crovidisin, a PIII snake venom metalloproteinase (SVMP) purified from venom of Crotalus viridis, exhibits collagen-binding activity and matrix metalloproteinase activity. Crovidisin selectively caused the detachment of ROS 17/2.8 osteosarcoma cells but not of primary cultured osteoblasts. On the other hand, triflavin, an RGD-dependent disintegrin purified from venom of Trimeresurus flavoviridis, did not cause the detachment of both osteoblasts and ROS 17/2.8 cells. Although ROS 17/2.8 cells detached from substratum after crovidisin treatment for 24 h, the loss of mitochondrial membrane potential was not observed unless a prolonged treatment for longer than 36 h. These results suggest that cultured primary rat osteoblasts and ROS 17/2.8 osteosarcoma cells possess different expression of integrins and matrix environment, and ROS 17/2.8 is much more susceptible to be detached by crovidisin. The matrix degradation by crovidisin may be responsible for the preferential detachment of ROS 17/2.8 osteosarcoma cells.
AuthorsChih-Hsin Tang, Rong-Sen Yang, Chao-Zong Liu, Tur-Fu Huang, Wen-Mei Fu
JournalToxicon : official journal of the International Society on Toxinology (Toxicon) Vol. 43 Issue 1 Pg. 11-20 (Jan 2004) ISSN: 0041-0101 [Print] England
PMID15037024 (Publication Type: Comparative Study, Journal Article, Research Support, Non-U.S. Gov't)
Chemical References
  • Carrier Proteins
  • Crotalid Venoms
  • Extracellular Matrix Proteins
  • Fibronectins
  • Integrins
  • Peptides
  • Reptilian Proteins
  • triflavin
  • Collagen
  • Metalloproteases
  • crovidisin protein, Crotalus viridis
Topics
  • Animals
  • Carrier Proteins (metabolism)
  • Cell Adhesion (drug effects)
  • Collagen (metabolism)
  • Crotalid Venoms (pharmacology)
  • Extracellular Matrix Proteins (metabolism)
  • Fibronectins (metabolism)
  • Integrins (metabolism)
  • Metalloproteases (pharmacology)
  • Osteoblasts (metabolism)
  • Osteosarcoma (metabolism, pathology)
  • Peptides (metabolism)
  • Rats
  • Reptilian Proteins
  • Tumor Cells, Cultured

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