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Unraveling the mysteries of serum albumin-more than just a serum protein.

Merlot AM, Kalinowski DS, Richardson DR - Front Physiol (2014)

Bottom Line: Considering this, there is renewed interest in isolating and characterizing albumin-binding proteins or receptors on the plasma membrane that are responsible for albumin uptake.Initially, the cellular uptake and intracellular localization of albumin was unknown due to the large confinement of the protein within the vascular and interstitial compartment of the body.Studies have since assessed the intracellular localization of albumin in order to understand the mechanisms and pathways responsible for its uptake, distribution and catabolism in multiple tissues, and this is reviewed herein.

View Article: PubMed Central - PubMed

Affiliation: Molecular Pharmacology and Pathology Program, Department of Pathology, Faculty of Medicine, Bosch Institute, The University of Sydney Sydney, NSW, Australia.

ABSTRACT
Serum albumin is a multi-functional protein that is able to bind and transport numerous endogenous and exogenous compounds. The development of albumin drug carriers is gaining increasing importance in the targeted delivery of cancer therapy, particularly as a result of the market approval of the paclitaxel-loaded albumin nanoparticle, Abraxane®. Considering this, there is renewed interest in isolating and characterizing albumin-binding proteins or receptors on the plasma membrane that are responsible for albumin uptake. Initially, the cellular uptake and intracellular localization of albumin was unknown due to the large confinement of the protein within the vascular and interstitial compartment of the body. Studies have since assessed the intracellular localization of albumin in order to understand the mechanisms and pathways responsible for its uptake, distribution and catabolism in multiple tissues, and this is reviewed herein.

No MeSH data available.


Related in: MedlinePlus

Schematic representation of (A) normal and (B) tumor vasculature. Normal tissue is composed of mature, organized blood vessels, while tumor tissue consists of immature, leaky and tortuous vessels. The altered organization of tumor vasculature and disorganized lymphatic network results in vascular leakage and the accumulation of macromolecules (>40 kDa) within the interstitium and is known as the enhanced permeation and retention (EPR) effect. Adapted by permission from Macmillan Publishers Ltd: Nature Medicine (Jain, 2001), copyright (2001).
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Figure 2: Schematic representation of (A) normal and (B) tumor vasculature. Normal tissue is composed of mature, organized blood vessels, while tumor tissue consists of immature, leaky and tortuous vessels. The altered organization of tumor vasculature and disorganized lymphatic network results in vascular leakage and the accumulation of macromolecules (>40 kDa) within the interstitium and is known as the enhanced permeation and retention (EPR) effect. Adapted by permission from Macmillan Publishers Ltd: Nature Medicine (Jain, 2001), copyright (2001).

Mentions: Solid tumors commonly possess an immature, highly permeable vasculature that is acted upon by vascular permeability-enhancing factors (e.g., nitric oxide) (Carmeliet and Jain, 2000; Maeda et al., 2000; Greish, 2007; van der Veldt et al., 2008). However, despite this there is generally insufficient lymphatic drainage (Carmeliet and Jain, 2000; Maeda et al., 2000; Greish, 2007). This subsequently results in an accumulation of macromolecules (>40 kDa) within the tumor interstitium, and this is known as the enhanced permeation and retention effect (Figure 2) (Maeda et al., 2000; Greish, 2007). Of interest, Matsumura and Maeda (1986) demonstrated that an intravenously injected Evans blue-albumin complex accumulated in sarcoma 180 tumors of ddY mice. The retention of albumin in tumors has since been observed in various experimental solid tumors (e.g., sarcoma, ovarian carcinoma, Novikof hepatoma, etc.) using radiolabeled- or dye-complexed serum albumin (Peterson and Appelgren, 1973; Sinn et al., 1990; Andersson et al., 1991; Schilling et al., 1992; Stehle et al., 1997; Wunder et al., 1997).


Unraveling the mysteries of serum albumin-more than just a serum protein.

Merlot AM, Kalinowski DS, Richardson DR - Front Physiol (2014)

Schematic representation of (A) normal and (B) tumor vasculature. Normal tissue is composed of mature, organized blood vessels, while tumor tissue consists of immature, leaky and tortuous vessels. The altered organization of tumor vasculature and disorganized lymphatic network results in vascular leakage and the accumulation of macromolecules (>40 kDa) within the interstitium and is known as the enhanced permeation and retention (EPR) effect. Adapted by permission from Macmillan Publishers Ltd: Nature Medicine (Jain, 2001), copyright (2001).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4129365&req=5

Figure 2: Schematic representation of (A) normal and (B) tumor vasculature. Normal tissue is composed of mature, organized blood vessels, while tumor tissue consists of immature, leaky and tortuous vessels. The altered organization of tumor vasculature and disorganized lymphatic network results in vascular leakage and the accumulation of macromolecules (>40 kDa) within the interstitium and is known as the enhanced permeation and retention (EPR) effect. Adapted by permission from Macmillan Publishers Ltd: Nature Medicine (Jain, 2001), copyright (2001).
Mentions: Solid tumors commonly possess an immature, highly permeable vasculature that is acted upon by vascular permeability-enhancing factors (e.g., nitric oxide) (Carmeliet and Jain, 2000; Maeda et al., 2000; Greish, 2007; van der Veldt et al., 2008). However, despite this there is generally insufficient lymphatic drainage (Carmeliet and Jain, 2000; Maeda et al., 2000; Greish, 2007). This subsequently results in an accumulation of macromolecules (>40 kDa) within the tumor interstitium, and this is known as the enhanced permeation and retention effect (Figure 2) (Maeda et al., 2000; Greish, 2007). Of interest, Matsumura and Maeda (1986) demonstrated that an intravenously injected Evans blue-albumin complex accumulated in sarcoma 180 tumors of ddY mice. The retention of albumin in tumors has since been observed in various experimental solid tumors (e.g., sarcoma, ovarian carcinoma, Novikof hepatoma, etc.) using radiolabeled- or dye-complexed serum albumin (Peterson and Appelgren, 1973; Sinn et al., 1990; Andersson et al., 1991; Schilling et al., 1992; Stehle et al., 1997; Wunder et al., 1997).

Bottom Line: Considering this, there is renewed interest in isolating and characterizing albumin-binding proteins or receptors on the plasma membrane that are responsible for albumin uptake.Initially, the cellular uptake and intracellular localization of albumin was unknown due to the large confinement of the protein within the vascular and interstitial compartment of the body.Studies have since assessed the intracellular localization of albumin in order to understand the mechanisms and pathways responsible for its uptake, distribution and catabolism in multiple tissues, and this is reviewed herein.

View Article: PubMed Central - PubMed

Affiliation: Molecular Pharmacology and Pathology Program, Department of Pathology, Faculty of Medicine, Bosch Institute, The University of Sydney Sydney, NSW, Australia.

ABSTRACT
Serum albumin is a multi-functional protein that is able to bind and transport numerous endogenous and exogenous compounds. The development of albumin drug carriers is gaining increasing importance in the targeted delivery of cancer therapy, particularly as a result of the market approval of the paclitaxel-loaded albumin nanoparticle, Abraxane®. Considering this, there is renewed interest in isolating and characterizing albumin-binding proteins or receptors on the plasma membrane that are responsible for albumin uptake. Initially, the cellular uptake and intracellular localization of albumin was unknown due to the large confinement of the protein within the vascular and interstitial compartment of the body. Studies have since assessed the intracellular localization of albumin in order to understand the mechanisms and pathways responsible for its uptake, distribution and catabolism in multiple tissues, and this is reviewed herein.

No MeSH data available.


Related in: MedlinePlus