Hspgs Proteins

 Creative BioMart Hspgs Proteins Product List
 Hspgs Proteins Background

Heparan Sulfate Proteoglycans (HSPGs)

Heparan sulfate proteoglycans have been shown to mediate cell entry for positively charged tri-platinum compounds. Due to the fact that nonaarginine is the most efficiently transported ‘protein transduction domain’, Silva et al. used a TAMRA (5- (and 6-) carboxytetramethylrhodamine) tagged nonaarginine to investigate how different platinum drugs competed with the nonaarginine for cellular internalization in wild type CHO cells. The neutral platinum compounds cisplatin and oxaliplatin did not inhibit the internalization of the nonaarginine. However, the positively charged tri-platinum compounds BBR3464, AH44 and Triplatin NC (aka AH78) prevented internalization of the nonaarginine in a charge-dependent manner. BBR3464 with a charge of +4 and AH44 with a charge of +6 decreased the nonaarginine internalization while Triplatin NC with a charge of +8 completely inhibited internalization of the nonaarginine. This was also examined in two cancer cell lines: the human colon carcinoma HCT116 and the osteosarcoma SAOS-2. Interestingly, the positively charged tri-platinum drugs showed increased inhibition of nonaarginine internalization in the tumor cell lines compared to the normal CHO cells. This suggests that these drugs may have some tumor selectivity. To confirm that heparan sulfate proteoglycans were responsible for these observations, Silva et al. investigated the cellular accumulation of the platinum drugs in CHO cells, heparan-sulfate deficient CHO cells and heparan- and chondroitin-sulfate deficient CHO cells. The cellular accumulation of BBR3464, AH44 and Triplatin NC was reduced in the CHO mutants confirming the role of proteoglycans in the uptake of positively charged platinum drugs. Furthermore, endocytosis is known to be a mechanism of cell entry for heparan sulfate proteoglycans. Silva et al. demonstrated that macropinocytosis, a type of endocytosis, is responsible for the uptake of Triplatin NC and to a lesser extent BBR3464.


HSPG2 is a 466kDa multi-domain heparan sulfate proteoglycan (HSPG) with a diverse tissue distribution and various biological functions, including cell adhesion, growth factor binding, and modulation of apoptosis. HSPG2 is a molecule that contains two to three GAG side chains at its N-terminus and sometimes one at its C-terminus. Both HSPG2 transcript and protein are highly expressed in cartilaginous regions of developing mouse embryos. Initially, HSPG2 is detected at low levels in precartilaginous areas of embryonic day 12.5. HSPG2 protein accumulates through embryonic day 15.5 a stage at which high levels are detected in cartilage primordia. Elevated levels of HSPG2 transcript at embryonic day 14.5 and decreased to initial levels by embryonic day 15.5 suggesting that HSPG2 may provide a source of HS chains for growth factors (GFs) to bind to during chondrogenesis. It is important to note that HS-bound GFs first must be liberated from the pericellular matrix of cartilage in order to interact with their receptors, and mediate downstream signaling events. Since HPSE has the ability to enzymatically release HS chains, HPSE may be a regulator of efficient growth factor delivery. Numerous studies within the Carson/Farach-Carson laboratory demonstrate the essential role of HSPG2 domain I, decorated with three glycosaminoglycan (GAG) chains, in aggregate formation, early chondrogenesis, and growth factor delivery.