The role of angiogenesis, vascular maturation, regression and stroma infiltration in dormancy and growth of XXXX spheroids.

@entity43 @entity32489 @entity851 @entity3113 @entity19 @entity5
@entity32489 @entity43 multicellular spheroids xenografted subcutaneously in CD-1 @entity19 @entity851 , or dormancy, of up to 52 days. In the study reported here, implanted @entity32489 spheroids were used for testing the role of angiogenesis and vascular maturation in triggering the @entity5 progression. The kinetics and impact of neovascular maturation and functionality, in dormancy, and growth of @entity32489 spheroid xenografts were studied noninvasively by BOLD contrast MRI. MR data were supported by histologic staining for biotinylated albumin as a blood pool marker and @entity3113 ( @entity3113 ) as marker for perivascular mural cells. Although the @entity5 periphery showed higher levels of total and mature vasculature than normal skin, the fraction of mature out of the total vessels as detected by MRI vascular maturation index (VMI(MRI)) was significantly lower in the @entity5 both before and after @entity5 exit from dormancy. The neovasculature induced by the implanted spheroid was unstable and showed cycles of vessel growth and regression. Surprisingly, this instability was not restricted to the immature vessels, but rather included also regression of mature vessels. During dormancy, neovasculature was predominantly peripheral with no infiltration into the implanted spheroid. Infiltration of @entity3113 positive stroma cells into the spheroid was associated with functional vascularization and @entity5 growth. Thus, stroma infiltration and vascular maturation are an important checkpoint linking the angiogenic switch with @entity5 progression.
