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Cell and molecular biology underpinning the effects of PEDF on cancers in general and osteosarcoma in particular.

Chandolu V, Dass CR - J. Biomed. Biotechnol. (2012)

Bottom Line: PEDF is a 50 kDa glycoprotein and is a potent inhibitor of angiogenesis, via its ability to decrease proliferation and migration of endothelial cells.This paper critically examines the anticancer activities of PEDF via its role in antiangiogenesis, apoptosis-mediated tumor suppression, and increased tumor cell differentiation.Recently, an orthotopic model of osteosarcoma was used to show that treatment with PEDF had the greatest impact on metastases, warranting an evaluation of PEDF efficacy in other types of cancers.

View Article: PubMed Central - PubMed

Affiliation: School of Biomedical and Health Sciences, Victoria University, Building 6, St Albans, VIC 3021, Australia.

ABSTRACT
Cancer is becoming an increasingly common disease in which abnormal cells aggressively grow, invade, and metastasize. In this paper, we review the biological functions of PEDF (pigmented epithelium-derived factor) against cancer, with a focus on a particular type of bone cancer called osteosarcoma. PEDF is a 50 kDa glycoprotein and is a potent inhibitor of angiogenesis, via its ability to decrease proliferation and migration of endothelial cells. This paper critically examines the anticancer activities of PEDF via its role in antiangiogenesis, apoptosis-mediated tumor suppression, and increased tumor cell differentiation. Recently, an orthotopic model of osteosarcoma was used to show that treatment with PEDF had the greatest impact on metastases, warranting an evaluation of PEDF efficacy in other types of cancers.

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Related in: MedlinePlus

PEDF apoptotic pathways. This schematic chart of apoptotic pathways represents concise information from various sources [5, 14–17]. PEDF apoptotic pathways. PEDF has been noted to induce apoptosis in mammalian cells via these pathways. It can directly stimulate Bax activity, inhibit Bcl-2, signal through PPARγ to activate p53, signal through p38, FasL, and finally through JNK to block c-FLIP. All these pathways culminate in apoptosis.
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fig2: PEDF apoptotic pathways. This schematic chart of apoptotic pathways represents concise information from various sources [5, 14–17]. PEDF apoptotic pathways. PEDF has been noted to induce apoptosis in mammalian cells via these pathways. It can directly stimulate Bax activity, inhibit Bcl-2, signal through PPARγ to activate p53, signal through p38, FasL, and finally through JNK to block c-FLIP. All these pathways culminate in apoptosis.

Mentions: The human PEDF gene has been mapped, and it encodes a 418 amino acid protein [11]. It has an asymmetrical charge distribution, with a high density of basic residues concentrated on one side and of acidic residues on the opposite side. Negatively charged acidic PEDF binds to collagen, lacks neurotrophic activity, and may confer antiangiogenic properties (Figure 1). Mutational studies have shown that positively charged amino acids and negatively-charged amino acids are responsible for heparin and collagen binding, respectively [12, 13]. There are three phosphorylation sites identified which collectively induce antiangiogenic and neurotrophic activities. A 34-mer peptide and 44-mer peptide are the two major functional epitopes identified (as shown in Figure 2) to date. The 34-mer peptide induces apoptosis, blocks endothelial cell migration and corneal angiogenesis, whereas the 44-mer peptide displays neurotrophic function and the ability to block vascular leakage.


Cell and molecular biology underpinning the effects of PEDF on cancers in general and osteosarcoma in particular.

Chandolu V, Dass CR - J. Biomed. Biotechnol. (2012)

PEDF apoptotic pathways. This schematic chart of apoptotic pathways represents concise information from various sources [5, 14–17]. PEDF apoptotic pathways. PEDF has been noted to induce apoptosis in mammalian cells via these pathways. It can directly stimulate Bax activity, inhibit Bcl-2, signal through PPARγ to activate p53, signal through p38, FasL, and finally through JNK to block c-FLIP. All these pathways culminate in apoptosis.
© Copyright Policy - open-access
Related In: Results  -  Collection

Show All Figures
getmorefigures.php?uid=PMC3368432&req=5

fig2: PEDF apoptotic pathways. This schematic chart of apoptotic pathways represents concise information from various sources [5, 14–17]. PEDF apoptotic pathways. PEDF has been noted to induce apoptosis in mammalian cells via these pathways. It can directly stimulate Bax activity, inhibit Bcl-2, signal through PPARγ to activate p53, signal through p38, FasL, and finally through JNK to block c-FLIP. All these pathways culminate in apoptosis.
Mentions: The human PEDF gene has been mapped, and it encodes a 418 amino acid protein [11]. It has an asymmetrical charge distribution, with a high density of basic residues concentrated on one side and of acidic residues on the opposite side. Negatively charged acidic PEDF binds to collagen, lacks neurotrophic activity, and may confer antiangiogenic properties (Figure 1). Mutational studies have shown that positively charged amino acids and negatively-charged amino acids are responsible for heparin and collagen binding, respectively [12, 13]. There are three phosphorylation sites identified which collectively induce antiangiogenic and neurotrophic activities. A 34-mer peptide and 44-mer peptide are the two major functional epitopes identified (as shown in Figure 2) to date. The 34-mer peptide induces apoptosis, blocks endothelial cell migration and corneal angiogenesis, whereas the 44-mer peptide displays neurotrophic function and the ability to block vascular leakage.

Bottom Line: PEDF is a 50 kDa glycoprotein and is a potent inhibitor of angiogenesis, via its ability to decrease proliferation and migration of endothelial cells.This paper critically examines the anticancer activities of PEDF via its role in antiangiogenesis, apoptosis-mediated tumor suppression, and increased tumor cell differentiation.Recently, an orthotopic model of osteosarcoma was used to show that treatment with PEDF had the greatest impact on metastases, warranting an evaluation of PEDF efficacy in other types of cancers.

View Article: PubMed Central - PubMed

Affiliation: School of Biomedical and Health Sciences, Victoria University, Building 6, St Albans, VIC 3021, Australia.

ABSTRACT
Cancer is becoming an increasingly common disease in which abnormal cells aggressively grow, invade, and metastasize. In this paper, we review the biological functions of PEDF (pigmented epithelium-derived factor) against cancer, with a focus on a particular type of bone cancer called osteosarcoma. PEDF is a 50 kDa glycoprotein and is a potent inhibitor of angiogenesis, via its ability to decrease proliferation and migration of endothelial cells. This paper critically examines the anticancer activities of PEDF via its role in antiangiogenesis, apoptosis-mediated tumor suppression, and increased tumor cell differentiation. Recently, an orthotopic model of osteosarcoma was used to show that treatment with PEDF had the greatest impact on metastases, warranting an evaluation of PEDF efficacy in other types of cancers.

Show MeSH
Related in: MedlinePlus