Volume 1, Issue 3, September 2013, Page: 26-30
Predictive Role of αVβ3 Integrin, and VEGF in Colorectal Adenocarcinoma Progression in Iraqi Patients
Ibrahim Abdulmajeed Altamemi, Deparment of Medical microbiology, College of medicine, Al-Qadisiya University, Alqadisia, Iraq
Alaa Ghani Hussein, Department of Pathology, College of medicine, Alnahrain University, Baghdad, Iraq
Ahmed Raheem Rayshan, Deparment of Pathology, College of medicine, Al-Qadisiya University, Alqadisia, Iraq
Received: Sep. 13, 2013;       Published: Oct. 30, 2013
DOI: 10.11648/j.crj.20130103.11      View  3314      Downloads  166
Angiogenesis, the formation of new blood vessels from pre-existing ones, is enhanced in various pathological conditions including rheumatoid arthritis, diabetic retinopathy, and cancer development. Angiogenic processes are regulated by both growth factors, such as vascular endothelial growth factor (VEGF), and adhesion molecules, such as integrin. Understanding the molecular mechanisms that underlieregulation of angiogenesis especially VEGF function, is essential for the development of safe and effective antiangiogenic therapies. Thus, current study was aimedto investigate predictive role of β3 integrin and vascular endothelial growth factor (VEGF) protein expression in colorectal adenocarcinoma sample from Iraqi patients, through linking its expression with tumor histopathological variables (stage, grade, grade, andlymph node involvement), by using Immunohistochemicalstaining method. Study done on 35 colorectal cancer samples and their respective resection margins.Present study demonstrated that, the positive expression rate of integrin β3 and VEGF in non-tumorcolorectal mucosa (25.33333 ± 1.974842, and 32.4± 1.974842) was significantly lower than that of the colorectal cancer (CRC)tissue (76.47059± 2.878562, and 79.45714±2.293705; P < 0.05). Moreover, when CRC samples breakdown according to histopathological variables, In patients of stage C-D, poorly differentiated, and withlymph node (L.N)invasion, the positive expression rates of integrin β3 were significantly higher than those in patients of patients with stageA,B, well or moderately differentiated,and without lymphatic metastasis (P < 0.05, P < 0.05, and P < 0.05; P< 0.05, P< 0.05, and P< 0.05), respectively. In conclusion Integrin β3 and VEGF expression can synergistically enhance tumor angiogenesis, and may play a crucial role in invasion and metastasis of colorectal carcinoma. Therefore, they may be prognostic biomarkers and novel molecular therapeutic targets.
Colorectal Cancer, Angiogenesis, VEGF
To cite this article
Ibrahim Abdulmajeed Altamemi, Alaa Ghani Hussein, Ahmed Raheem Rayshan, Predictive Role of αVβ3 Integrin, and VEGF in Colorectal Adenocarcinoma Progression in Iraqi Patients, Cancer Research Journal. Vol. 1, No. 3, 2013, pp. 26-30. doi: 10.11648/j.crj.20130103.11
Risau, W. (1997) Mechanisms of angiogenesis. Nature 386, 671–674
Carmeliet, P., and Jain, R. K. (2000) Angiogenesis in cancer and other diseases. Nature 407, 249–257
Yancopoulos, G. D., Davis, S., Gale, N. W., Rudge, J. S., Wiegand, S. J., and Holash, J. (2000) Vascular-specific growth factors and blood vessel formation. Nature 407, 242–248
Hynes, R. O., Bader, B. L., and Hodivala-Dilke, K. (1999) Integrins in vascular development. Braz. J. Med. Biol. Res. 32, 501–510
Ferrara, N. (1999) Vascular endothelial growth factor: molecular and biological aspects. Curr.Top.Microbiol.Immunol.237, 1–30
Dvorak, H. F., Nagy, J. A., Feng, D., Brown, L. F., and Dvorak, A. M. (1999) Vascular permeability factor/vascular endothelial growth factor and the significance of microvascular hyperpermeability in angiogenesis. Curr.Top.Microbiol.Immunol.237, 97–132
Brooks, P. C., Clark, R. A., and Cheresh, D. A. (1994) Requirement of vascular integrin alpha v beta 3 for angiogenesis. Science 264, 569–571
Hood JD, Cheresh DA. Role of integrins in cell invasion and migration.Nat Rev Cancer 2002; 2: 91-100
Hwang R, Varner J. The role of integrins in tumor angiogenesis.HematolOncolClin North Am 2004; 18: 991-1006, vii
ContiJA, Kendall TJ, Bateman A, et al. The desmoplastic reaction surrounding hepatic colorectal adenocarcinoma metastases aids tumour growth and survival via αvintegrinligation.ClinCancerRes2008;14:6405^13.
Astler V. B. and Coller F. A., 1954. The prognostic significance of direct extension of carcinoma of the colon and rectum. Ann Surg, 139: 846-847.
Reynolds AR, Reynolds LE, Nagel TE, Lively JC, Robinson SD, Hicklin DJ, Bodary SC, Hodivala-Dilke KM. Elevated Flk1 (vascular endothelial growth factor receptor 2) signaling mediates enhanced angiogenesis in beta3-integrin-deficient mice. Cancer Res 2004; 64: 8643-8650
Laakkonen P, Waltari M, Holopainen T, Takahashi T, Pytowski B, Steiner P, Hicklin D, Persaud K, Tonra JR, Witte L, Alitalo K. Vascular endothelial growth factor receptor 3 is involved in tumor angiogenesis and growth. Cancer Res 2007; 67: 593-599
Des Guetz G, Uzzan B, Nicolas P, et al. Microvessel density and VEGF expression are prognostic factors in colorectal cancer. Meta-analysis of the literature. Br J Cancer 2006; 94: 1823-32.
Liang JF, Wang HK, Xiao H, Li N, Cheng CX, Zhao YZ, Ma YB, Gao JZ, Bai RB, Zheng HX. Relationship and prognostic significance of SPARC and VEGF protein expression in colon cancer. JExp Clin Cancer Res 2010;29:71
Levy N.S, Goldberg-cohen I, and Levy A.P., 2004. Hypoxic regulation of VEGF.VEGF in Colon Cancer.VEGF and Cancer, chapter eight.Edited by Judith H. Harmey.
Guba M, Seeliger H, Karl-Walter Jauch K.W and Bruns C.J., 2004. VEGF in Colon Cancer.VEGF and Cancer, chapter eight.Edited by Judith H. Harmey.
18.Trikha, M., Timar, J., Zacharek, A., Nemeth, J. A., Cai, Y., Dome, B., Somlai, B., Raso, E., Ladanyi, A., Honn, K. V. (2002) Role for β3 integrins in human melanoma growth and survival. Int. J. Cancer 101, 156-167.
Mizejewski GJ. Role of integrins in cancer: survey of expression patterns. ProcSoc ExpBiol Med 1999; 222: 124-138
Risau W. Mechanisms of angiogenesis. Nature 1997; 386: 671-674
Cooper CR, Chay CH, Pienta KJ. The role of alpha(v)beta(3) in prostate cancer progression. Neoplasia2002; 4: 191-194
22.ReinmuthN, Liu W, Ahmad SA, Fan F, Stoeltzing O, Parikh AA, Bucana CD, Gallick GE, Nickols MA, Westlin WF, Ellis LM. Alphavbeta3 integrin antagonist S247 decreases colon cancer metastasis and angiogenesis and improves survival inmice. Cancer Res 2003; 63: 2079-2087
Stupack, D. G., Puente, X. S., Boutsaboualoy, S., Storgard, C. M., and Cheresh, D. A.(2001) Apoptosis of adherent cells by recruitment of caspase-8 to unligated integrins. J. Cell Biol. 155, 459–470
Vlahakis NE, Young BA, Atakilit A, Hawkridge AE, Issaka RB, Boudreau N,et al. Integrin α9β1 directly binds to vascular endothelial growth factor (VEGF)-A and contributes to VEGF-A-induced angiogenesis. J BiolChem 2007;282:15187–96.
Hutchings H, Ortega N, Plouët J. Extracellular matrix-bound vascular endothelialgrowth factor promotes endothelial cell adhesion, migration, and survivalthrough integrin ligation. FASEB J 2003;11:1520–2.
Soldi R, Mitola S, Strasly M, Defilippi P, Tarone G, Bussolino F. Role of αvβ3integrin in the activation of vascular endothelial growth factor receptor-2.EMBO J 1999;8:882–92.
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