Stanniocalcin 2 (STC2) is a secreted
glycoprotein of as yet unknown functions. We investigated STC2 in human
neuroblastoma, the most common solid extra-cranial
tumor of infancy. In primary
tumor samples, we found that expression of STC2 is associated with the metastatic Stages 4 and 4s and MYCN expression. In vitro, however, we demonstrate that cell proliferation is reduced by STC2 due to an increase in the basal apoptosis rate of the transfected cells. On the other hand, in vitro assays showed that STC2-transfected
neuroblastoma cells have an increased invasive potential and display higher activity of
collagen-degrading
matrix metalloproteinase 2 (MMP2). Using experimental
tumors on the chick chorioallantoic membrane (CAM), we observed that STC2 expressing cells show signs of emigration from the solid
tumor and destroy blood vessels of the CAM, giving rise to massively
bleeding tumors. Erosion of blood vessels was also seen when purified STC2
protein was applied on the CAM. Taken together, we demonstrate a dual role for STC2 in
neuroblastoma. It reduces proliferation of
tumor cells in vitro, but increases the invasive potential and induces
bleeding, and thereby may facilitate early
metastasis. The potential of STC2 as a
surrogate marker for metastatic
neuroblastoma calls for further investigation.