RGD-Binding Integrins in Prostate Cancer: Expression Patterns and Therapeutic Prospects against Bone Metastasis
Abstract
:Abbreviations
Akt | protein kinase B |
BBN | bombesin |
BSP | bone sialoprotein |
DOTA | 1,4,7,10-tetraazacyclododecane-1,4,7,10-tetraacetic acid |
DSPP | dental sialophosphoprotein |
ECM | extracellular matrix |
EGFR | epidermal growth factor receptor |
EMT | epithelial mesenchymal transition |
ERK | extracellular signal-regulated kinase |
FACS | fluorescence activated cell sorting |
FAK | focal adhesion kinase |
Fg | fibrinogen |
Fn | fibronectin |
GRPR | gastrin releasing peptide receptor |
Hsp90 | heat shock protein 90 |
HUVEC | human umbilical vein endothelial cell |
IGF-1R | insulin-like growth factor type 1 receptor |
LAP | latency associated peptide |
MEK | mitogen-activated protein kinase/extracellular signal-regulated kinase kinase |
MMP | matrix metalloproteinase |
MRI | magnetic resonance imaging |
NODA | 1,4,7-triazacyclononane-1,4-diacetic acid |
NOTA | 1,4,7-triazacyclononane-1,4,7-triacetic acid |
PET | positron emission tomography |
PI3K | phosphoinositide 3-kinase |
PSA | prostate specific antigen |
OPN | osteopontin |
SIBLING | small integrin binding N-linked glycoprotein |
SMART | Simultaneously Multiple Aptamers and RGD Targeting |
SPARC | secreted protein acidic and rich in cysteine |
TCIPA | tumour cell-induced platelet aggregation |
TGF-β | transforming growth factor-β |
TNF-α | tumour necrosis factor-α |
VEGF(R) | vascular endothelial growth factor (receptor) |
Vn | vitronectin |
vWF | von Willebrand factor |
1. Introduction
Integrin | Common Ligands | Major physiological roles |
---|---|---|
αvβ1 | Fibrinogen (Fg), Fibronectin (Fn), Vitronectin (Vn), Osteopontin (OPN), LAP-TGF-β | |
αvβ3 | Fg, Von Willebrand factor (vWF), Fn, Vn, Bone sialoprotein (BSP), OPN, LAP-TGF-β | Angiogenesis Bone resorption |
αvβ5 | Fn, Vn, BSP, LAP-TGF-β | Angiogenesis Vascular permeability |
αvβ6 | Fn, Vn, OPN, LAP-TGF-β | Lung development and physiology TGF-β activation |
αvβ8 | Vn, LAP-TGF-β | TGF-β activation Angiogenesis Brain development |
α5β1 | Fn, OPN | Angiogenesis |
α8β1 | Fn, Vn, Tenascin, OPN, LAP-TGF-β, Nephronectin | Kidney and lung development Hair cell differentiation and function |
αIIbβ3 | Fg, Fn, Vn, vWF | Platelet aggregation |
2. Expression of RGD-Binding Integrins in Prostate Cancer
2.1. Clinical Prostate Adenocarcinoma
Integrin | Expressed in normal prostate tissue? | Expressed in primary prostate tumours? | Expressed in metastases? | Reference |
---|---|---|---|---|
αvβ1 | Yes | [41] | ||
αvβ3 | No | Yes | Yes | [39,42,43,44,45,46] |
αvβ5 | No | Yes | Yes | [45,47] |
αvβ6 | No | Yes | [47,48] | |
αvβ8 | No | No | [47] | |
α5β1 | Yes | Reduced | Yes | [44,49] |
αIIbβ3 | No | Yes | Yes | [42,50] |
2.2. Preclinical Models of Prostate Cancer
Cell line | αIIbβ3 | αvβ3 | αvβ1 | αvβ5 | α5β1 | αvβ6 | αvβ8 | Reference |
---|---|---|---|---|---|---|---|---|
PC-3 | − | + | +++ | ++ | [58] | |||
PC-3 | − | ++ | ++ | [59] | ||||
PC-3 | − | ++ | +/− | + | [47] | |||
PC-3 | + | [34,50] | ||||||
PC-3 | ++ | [60] | ||||||
PC-3 | ++ | [61] | ||||||
PC-3 | ++ | ++ | ++ | ++ | [62] | |||
PC-3 | – | [63] | ||||||
PC-3 | ++ | [57] | ||||||
PC-3 | +++ | [64] | ||||||
PC-3 | +++ | +++ | [65] | |||||
DU145 | +/– | ++ | − | − | [47] | |||
DU145 | + | [34,50] | ||||||
DU145 | ++ | [66] | ||||||
DU145 | ++ | [61] | ||||||
DU145 | ++ | [48] | ||||||
DU145 | + | [63] | ||||||
LNCaP | ++ | [60] | ||||||
LNCaP | ++ | [61] | ||||||
LNCaP | − | + | ns | +/− | [39] | |||
LNCaP | ++ | [63] | ||||||
LNCaP | ++ | [64] | ||||||
C4-2 | ++ | [60] | ||||||
C4-2 | ++ | [64] |
Cell line | αIIb | αv | α5 | β1 | β3 | β5 | β6 | β8 | Reference |
---|---|---|---|---|---|---|---|---|---|
PC-3 | +++ | +++ | +++ | + | − | [39] | |||
PC-3 | + | ++ | +++ | + | +/− | [67] | |||
PC-3 | +/− | ns | [68] | ||||||
PC-3 | − | + | + | +++ | +/− | [69] | |||
PC-3 | +++ | +++ | [64] | ||||||
PC-3 | + | ++ | + | [70] | |||||
DU145 | + | ++ | +++ | +/− | +/− | [67] | |||
DU145 | + | + | [71] | ||||||
DU145 | − | + | ++ | ++ | +/− | +/− | [69] | ||
LNCaP | ++ | +++ | − | + | +/− | [39] | |||
LNCaP | ++ | ++ | + | [72] | |||||
LNCaP | ++ | − | [64] | ||||||
LNCaP | + | + | − | [70] | |||||
C4-2 | +++ | [40] | |||||||
C4-2 | ++ | ++ | + | [72] | |||||
C4-2 | +++ | − | [64] | ||||||
DuPro1 | − | + | + | ++ | − | + | [69] |
3. Consequences of Integrin Expression in Prostate Cancer
3.1. αv Subfamily Integrins
3.2. αIIbβ3
3.3. α5β1
3.4. Angiogenesis
3.5. Epithelial-Mesenchymal Transition
3.6. Laminin Binding Integrins
4. Changes in Integrin Expression in Response to Therapy
Drug | Cell line | Integrin subunits upregulated | Integrin subunits downregulated | Reference |
---|---|---|---|---|
Zoledronic acid | PC-3 | β1 | β4 | [164] |
Doxazosin | PC-3 | β8 (mRNA) | α5, αv, β1, β5, β6 (mRNA) | [165] |
Camptothecin | PC-3 | αv, β3, β5 | [166] | |
Genistein | DU145 | α2, α3, β1 | [167] | |
Valproic acid (VPA) | PC-3 | α1, α3 | α6, β3 | [168,169,170,171] |
VPA + interferon-α | PC-3 | α1, α3, β1 | α5, α6, β4 | [168] |
AEE788 | PC-3 | α1 | α5 | [70,170,171] |
RAD001 | PC-3 | α2, β3 | α1, α5 | [70,169,171] |
AEE877+ RAD001 | PC-3 | α2, β3 | α1, α5 | [70] |
VPA+RAD001 | PC-3 | α1, α2, α3 | α5, α6, β3 | [169] |
VPA+AEE788 | PC-3 | α1, α3 | α5, α6, β3 | [170] |
VPA+AEE788+RAD001 | PC-3 | α1, α2, α3, β1 | α5, α6, β3 | [171] |
VPA | LNCaP | α2, α3, α5, α6, β1 | [168,169,170,171] | |
VPA + interferon-α | LNCaP | α2, α3, α5, α6, β1, β3, β4 | [168] | |
AEE788 | LNCaP | α3 | α2, α6 | [70,171] |
RAD001 | LNCaP | α3 | β1 | [70,169,171] |
AEE877+ RAD001 | LNCaP | α3, α5, α6, β1 | [70] | |
VPA+RAD001 | LNCaP | α2, α3, α5, α6, β1 | [169] | |
VPA+AEE788 | LNCaP | α2, α3, α5, α6, β1 | [170] | |
VPA+AEE788+RAD001 | LNCaP | α2, α3, α5, α6, β1 | [171] |
5. RGD-Binding Integrin Antagonists in Prostate Cancer Therapy
5.1. Preclinical Studies
5.2. Clinical Trials
6. Integrin Targeting for Drug Delivery and Imaging
6.1. Drug Delivery
6.2. Imaging
7. Conclusions and Future Prospects
Acknowledgments
Conflict of Interest
References
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Sutherland, M.; Gordon, A.; Shnyder, S.D.; Patterson, L.H.; Sheldrake, H.M. RGD-Binding Integrins in Prostate Cancer: Expression Patterns and Therapeutic Prospects against Bone Metastasis. Cancers 2012, 4, 1106-1145. https://doi.org/10.3390/cancers4041106
Sutherland M, Gordon A, Shnyder SD, Patterson LH, Sheldrake HM. RGD-Binding Integrins in Prostate Cancer: Expression Patterns and Therapeutic Prospects against Bone Metastasis. Cancers. 2012; 4(4):1106-1145. https://doi.org/10.3390/cancers4041106
Chicago/Turabian StyleSutherland, Mark, Andrew Gordon, Steven D. Shnyder, Laurence H. Patterson, and Helen M. Sheldrake. 2012. "RGD-Binding Integrins in Prostate Cancer: Expression Patterns and Therapeutic Prospects against Bone Metastasis" Cancers 4, no. 4: 1106-1145. https://doi.org/10.3390/cancers4041106