Tension in Cancer
Abstract
:1. Introduction
2. Integrins
2.1. Structure and Ligand Affinity of Integrins
2.2. Integrin-Mediated Adhesion and Physical Forces
3. Interfering Integrin-ECM Interactions as a Potential Therapeutic Strategy
4. Changing the Tension in Cancer
4.1. Stroma-Driven, Integrin-Mediated Neoplastic Transformation
4.2. Matrix-Stiffening Regulates Malignancy by Enhancing Integrin-Dependent Mechano-Transduction
4.3. Matrix-Stiffening Induced Integrin-Signalling Drives Tumor Therapy Resistance
5. Conclusions and Future Perspectives
Acknowledgments
Author Contributions
Conflicts of Interest
References
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Integrin | Prototypic Ligands |
---|---|
α1β1 (CD49a, VLA1) | Collagen IV, I and IX |
α2β1 (CD49b, VLA2) | Collagen I, IV and IX |
α3β1 (CD49c, VLA3) | Laminin-511, -332, -211 |
α4β1 (CD49d, VLA4) | Fibronectin, VCAM-1 |
α5β1 (CD49e, VLA5) | Fibronectin |
α6β1 (CD49f, VLA6) | Laminin-511, -332, -111, -411 |
α7β1 | Laminin-511, -211, -411, -111 |
α8β1 | Fibronectin, vitronectin, |
α9β1 | Tenascin-C, VEGF-C, VEGF-D |
α10β1 | Collagen I, IV, II and IX |
α11β1 | Collagen I, IV and IX |
α6β4 | Laminin-332, -511 |
αvβ1 (CD51) | Fibronectin, vitronectin |
αvβ3 | Vitronectin, fibronectin, fibrinogen |
αvβ5 | Vitronectin |
αvβ6 | Fibronectin, TGF-β-LAP |
αvβ8 | Vitronectin, TGF-β-LAP |
αEβ7 (CD103, HML-1) | E-cadherin |
α4β7 | MadCAM-1, fibronectin, VCAM-1 |
αLβ2 (CD11a) | ICAM-1, -2, -3, -5 |
αMβ2 (CD11b) | Fibrinogen |
αXβ2 (CD11c) | Fibrinogen |
αDβ2 (CD11d) | ICAM-3, VCAM-1 |
αIIBβ3 (CD41) | Fibrinogen, fibronectin |
Target | Inhibitor | Clinical Trial | Ref. |
---|---|---|---|
α5β1 | ATN-161 (small peptide antagonist) | Phase II: patients with advanced solid malignancies | [73] |
α5β1 | Volociximab (mAb) | Phase I: patients with advanced solid malignancies | [68] |
α5β1 | Volociximab (mAb) | Phase II: patients with therapy-resistant epithelial ovarian cancer and primary peritoneal cancer | [69] |
αvβ3, αvβ5 | Cilengitide (EMD 121974) | Phase III: glioblastoma patients | [64] |
α5β1 | PF-04605412 (mAb) | Safety study: advanced solid tumors | [66] |
αvβ3 | Etaracizumab (MEDI-522) | Phase I: metastatic solid tumors | [74] |
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Löffek, S.; Franzke, C.-W.; Helfrich, I. Tension in Cancer. Int. J. Mol. Sci. 2016, 17, 1910. https://doi.org/10.3390/ijms17111910
Löffek S, Franzke C-W, Helfrich I. Tension in Cancer. International Journal of Molecular Sciences. 2016; 17(11):1910. https://doi.org/10.3390/ijms17111910
Chicago/Turabian StyleLöffek, Stefanie, Claus-Werner Franzke, and Iris Helfrich. 2016. "Tension in Cancer" International Journal of Molecular Sciences 17, no. 11: 1910. https://doi.org/10.3390/ijms17111910