Hyaluronan (HA), a secreted glycosaminoglycan component of extracellular matrices, is critical for cellular proliferation and motility during development. However, elevated circulating and cell-associated levels correlate with various types of @entity5 , including prostate. We have previously shown that aggressive PC3M-LN4 @entity263 cells synthesize excessive HA relative to @entity146 cells, and express correspondingly higher levels of the HA biosynthetic enzymes @entity4660 and @entity9907 . Inhibition of these enzymes by stable transfection of PC3M-LN4 cells with anti-sense @entity4660 or @entity9907 expression constructs diminishes HA synthesis and surface retention. In this report, we used these @entity8273 cell lines to examine the role of HA in tumorigenicity. Subcutaneous injection of @entity915 @entity19 with hyaluronan synthase (HAS) antisense-transfected cells produced @entity5 threefold to fourfold smaller than control transfectants. Tumors from HAS antisense transfectants were histologically @entity8273 relative to controls. @entity8273 corresponded to threefold reduced cell numbers per @entity5 , but comparable numbers of apoptotic and proliferative cells. Percentages of apoptotic cells in cultured transfectants were identical to those of control cells, but antisense inhibition of HA synthesis effected slower growth rate of cells in culture. Quantification of blood vessel density within @entity5 sections revealed 70 to 80% diminished vascularity of HAS antisense @entity5 . Collectively, the results suggest HAS overexpression by @entity263 cells may facilitate their growth and proliferation in a complex environment by enhancing intrinsic cell growth rates and promoting angiogenesis. Furthermore, this is the first report of a role for inhibition of HA synthesis in reducing @entity5 growth kinetics.

Inhibition of @entity263 cell hyaluronan synthesis impairs subcutaneous growth and vascularization in immunocompromised XXXX .

@entity8273 :: ('MESH:C565742', 'Disease') :: ['HA-deficient', 'HA deficiency'] @entity263 :: ('MESH:D011471', 'Disease') :: ['prostate tumor'] @entity146 :: ('MESH:D001523', 'Disease') :: ['less aggressive'] @entity5 :: ('MESH:D009369', 'Disease') :: ['tumor', 'cancer', 'tumors'] @entity4660 :: ('3037', 'Gene') :: ['HAS2'] @entity19 :: ('10090', 'Species') :: ['mice'] @entity915 :: ('MESH:D053632', 'Disease') :: ['SCID'] @entity9907 :: ('3038', 'Gene') :: ['HAS3']
@entity19 :: (10090,Species) :: ['mice']
