Sunday, February 1, 2015

Collagen XIX is strongly anti-tumorigenic

The NC1 domain of type XIX collagen inhibits in vivo melanoma growth.

Mol Cancer Ther. 2007 Feb;6(2):506-14.
The NC1 domain of type XIX collagen inhibits in vivo melanoma growth.
Type XIX collagen is a minor collagen that localizes to basement membrane zones, together with types IV, XV, and XVIII collagens. Because several NC1 COOH-terminal domains of other chains from basement membrane collagens were reported to exhibit antitumor activity, we decided to study the effects of the NC1(XIX) collagen domain on tumor progression using an experimental in vivo model of mouse melanoma. We observed a 70% reduction in tumor volume in NC1(XIX)-treated mice compared with the corresponding controls. Histologic examination of the tumors showed a strong decrease in tumor vascularization in treated mice. In vitro, NC1(XIX) inhibited the migrating capacity of tumor cells and their capacity to invade Matrigel. It also inhibited the capacity of human microvascular endothelial cells to form pseudotubes in Matrigel. This effect was accompanied by a strong inhibition of membrane type-1 matrix metalloproteinase (matrix metalloproteinase-14) and vascular endothelial growth factor expression. Collectively, our data indicate that the NC1 domain of type XIX collagen exerts antitumor activity. This effect is mediated by a strong inhibition of the invasive capacities of tumor cells and antiangiogenic effects. NC1(XIX) should now be considered as a new member of the basement membrane collagen-derived matrikine family with antitumor and antiangiogenic activity.
PMID: 17308049
 

The NC1 domain of type XIX collagen inhibits melanoma cell migration. 

Eur J Dermatol. 2010 Nov-Dec;20(6):712-8. doi: 10.1684/ejd.2010.1070. Epub 2010 Sep 14.
 The NC1 domain of type XIX collagen inhibits melanoma cell migration.
Type XIX collagen is a minor collagen that localizes to basement membrane zones. We previously demonstrated that the C-terminal NC1 domain of type XIX collagen inhibits tumor growth in vivo. In the present study, we analyzed the effects of the NC1(XIX) collagen domain on migratory behaviour of melanoma B16F10 cells. We found that NC1(XIX) do not inhibit melanoma cell proliferation. On the contrary, NC1(XIX) strongly inhibited the migratory capacities of melanoma cells in the scratch wound model and in Ibidi® devices: cell migration speed was 7.69 ± 1.49 μm/h for the controls vs 6.64 ± 0.82 μm/h for cells incubated with 30 μmol/L NC1(XIX) and 5.72 ± 0.67 μmol/h with 60 μmol/L NC1(XIX). Similar results were obtained with UACC 903 human melanoma cells. Further work will be necessary to elucidate the molecular mechanisms of this migration inhibition. It may, however, explain, at least partially, the inhibition of tumor growth that we observed in vivo.
PMID: 20840910
 
 

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