Albondin (gp60) and Secreted protein acidic and rich in cysteine (SPARC) (gp60/SPARC)

The gp60 receptor (albondin), caveolin-1-mediated caveolae, and Secreted Protein Acidic and Rich in Cysteine (SPARC) constitute a specialized transport pathway for albumin-bound substances (Schnitzer et al., Science, 1994). gp60 is a 60 kDa glycoprotein on the endothelial cell surface that binds albumin, initiating its internalization into caveolae (Tiruppathi et al., J Biol Chem, 1997). This process, dependent on the structural protein caveolin-1, facilitates the transcytosis of albumin across the vascular endothelium into the interstitial space. Once in the tumor microenvironment, albumin-bound molecules are sequestered by SPARC, a matricellular protein often overexpressed by tumor-associated fibroblasts and certain cancer cells (Desai et al., Clin Cancer Res, 2006). This biological mechanism is the primary target exploited by nanoparticle albumin-bound (nab) technology, such as nab-paclitaxel (Abraxane). By mimicking the natural transport of albumin, these drugs achieve higher intratumoral concentrations compared to traditional solvent-based formulations (Neuzillet et al., Cancer Metastasis Rev, 2013). The pathway allows for improved drug delivery while potentially reducing the systemic toxicity associated with surfactants like Cremophor EL. Clinical interest in this pathway also focuses on using SPARC expression as a potential biomarker for patient selection, although its predictive value remains a subject of debate. Overall, this multi-component system represents a sophisticated method for enhancing the therapeutic index of hydrophobic chemotherapeutic agents.

Other names

gp60 receptorAlbondinSecreted protein acidic and rich in cysteineOsteonectinBM-40Caveolin-1 mediated transport pathway

Facilitation of albumin-bound drug transcytosis across the endothelium via gp60 and caveolae, followed by sequestration in the tumor stroma by SPARC.