Although there are numerous reports of
carbohydrates enriched in
cancer cells, very few studies have addressed the functions of
carbohydrates present in normal cells that decrease in
cancer cells. It has been reported that core3 O-
glycans are synthesized in normal gastrointestinal cells but are down-regulated in
cancer cells. To determine the roles of core3 O-
glycans, we transfected PC3 and LNCaP
prostate cancer cells with beta3-N-acetylglucosaminyltransferase-6 (core3 synthase) required to synthesize core3 O-
glycans. Both engineered cell lines exhibited reduced migration and invasion through extracellular matrix components compared with mock-transfected cells. Moreover we found that
alpha2beta1 integrin acquired core3 O-
glycans in cells expressing core3 synthase with decreased maturation of
beta1 integrin, leading to decreased levels of the
alpha2beta1 integrin complex, decreased activation of
focal adhesion kinase, and reduced lamellipodia formation. Upon inoculation into the prostate of nude mice, PC3 cells expressing core3 O-
glycans produced much smaller
tumors without
metastasis to the surrounding lymph nodes in contrast to robust
tumor formation and
metastasis seen in mock-transfected PC3 cells. Similarly LNCaP cells expressing core3 O-
glycans barely produced subcutaneous
tumors in contrast to robust
tumor formation by mock-transfected LNCaP cells. These findings indicate that addition of core3 O-
glycans to beta1 and
alpha2 integrin subunits in
prostate cancer cells suppresses
tumor formation and
tumor metastasis.