Limits...
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.

Show MeSH

Related in: MedlinePlus

Types of cancers that PEDF has activity against.
© Copyright Policy - open-access
Related In: Results  -  Collection


getmorefigures.php?uid=PMC3368432&req=5

fig3: Types of cancers that PEDF has activity against.

Mentions: PEDF is known as a multifunctional protein which possesses potent antiangiogenic, neurotrophic, neuroprotective, immunosuppressive, and antitumorigenic properties (see Figure 3). Ek et al. [60] identified potential functional epitopes on the PEDF protein sequence and determined their antitumour activity in the human osteosarcoma cell line SaOS-2. They characterized the bioactivity of four synthetic peptides corresponding to sequences 40–64 (StVOrth-1), 78–102 (StVOrth-2), 90–114 (StVOrth-3), and 387–411 (StVOrth-4) of human PEDF using SaOS-2. They evaluated the antiproliferative effects of the peptides and found that StVOrth-2 exhibited the most significant anti-proliferative activity, with a reduction of 59% and 63% seen at day 5 with lower (5 nM) and higher (25 nM) concentrations, respectively. They examined the potential behind suppression of tumour cell invasion through Matrigel and found that all four peptides significantly decreased Matrigel invasion by greater that 50%. However StVOrth-4 provided that most consistent inhibition, with greater than 70% reduction observed at all concentrations. Ek et al. examined treatment with the PEDF-derived peptides for understanding the alteration of osteosarcoma cell adhesion to collagen (a potential mechanism in antimetastasis) and found that all four peptides considerably increased cell adhesion to collagen type 1, with StVOrth-3 demonstrating 53% greater ability than the other peptides. Prodifferentiation potential studies of the PEDF fragments in vitro revealed that administration of StVOrth-1, -2, and -3 significantly increased nodule formation in SaOS-2 cells. They further tested the in vivo activity of StVOrth-2 and StVOrth-3 in an orthotopic model of human osteosarcoma, using a model employing tumour cells premixed with peptides, then injected orthotopically. StVOrth-2 exhibited predominantly antiproliferation activity, while StVOrth-3 caused mainly increased collagen adhesion and VEGF suppression. The results of an efficacy study using sustained delivery of peptides in the orthotopic model of osteosarcoma is included in this issue [5, 54].


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)

Types of cancers that PEDF has activity against.
© Copyright Policy - open-access
Related In: Results  -  Collection

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

fig3: Types of cancers that PEDF has activity against.
Mentions: PEDF is known as a multifunctional protein which possesses potent antiangiogenic, neurotrophic, neuroprotective, immunosuppressive, and antitumorigenic properties (see Figure 3). Ek et al. [60] identified potential functional epitopes on the PEDF protein sequence and determined their antitumour activity in the human osteosarcoma cell line SaOS-2. They characterized the bioactivity of four synthetic peptides corresponding to sequences 40–64 (StVOrth-1), 78–102 (StVOrth-2), 90–114 (StVOrth-3), and 387–411 (StVOrth-4) of human PEDF using SaOS-2. They evaluated the antiproliferative effects of the peptides and found that StVOrth-2 exhibited the most significant anti-proliferative activity, with a reduction of 59% and 63% seen at day 5 with lower (5 nM) and higher (25 nM) concentrations, respectively. They examined the potential behind suppression of tumour cell invasion through Matrigel and found that all four peptides significantly decreased Matrigel invasion by greater that 50%. However StVOrth-4 provided that most consistent inhibition, with greater than 70% reduction observed at all concentrations. Ek et al. examined treatment with the PEDF-derived peptides for understanding the alteration of osteosarcoma cell adhesion to collagen (a potential mechanism in antimetastasis) and found that all four peptides considerably increased cell adhesion to collagen type 1, with StVOrth-3 demonstrating 53% greater ability than the other peptides. Prodifferentiation potential studies of the PEDF fragments in vitro revealed that administration of StVOrth-1, -2, and -3 significantly increased nodule formation in SaOS-2 cells. They further tested the in vivo activity of StVOrth-2 and StVOrth-3 in an orthotopic model of human osteosarcoma, using a model employing tumour cells premixed with peptides, then injected orthotopically. StVOrth-2 exhibited predominantly antiproliferation activity, while StVOrth-3 caused mainly increased collagen adhesion and VEGF suppression. The results of an efficacy study using sustained delivery of peptides in the orthotopic model of osteosarcoma is included in this issue [5, 54].

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