Co-expression of CXCR4 and CD133 in gastric neoplastic tissue and their correlation with clinicopathological factors and prognosis in gastric cancer
Purpose: Worldwide Gastric carcinoma considered as the second most common cause of cancer related death. Cancer stem cell plays significant role in prognosis and invasion of gastric cancer. CXCR4 is a chemokine receptor and plays an important role in self renewal, differentiation potential, and cell adhesion of cancer stem cell (CSC). On the other hand CD133 is a cell surface glycoprotein and could serve as a prognostic indicator for tumor re-growth, malignant progression, and patient survival. The aim of this study was to establish the expression pattern of CXCR4 and CD133 in gastric cancer tissues; and their correlation with clinicopathological factors like age and gender of patients, position, size and depth of tumor, lymphatic invasion and node metastasis.
Methods: Expression of CXCR4 and CD133 proteins were assessed by immunohistochemical and immunofluorescence staining of paraffin–embedded tissues, and followed by RT-PCR in 90 tumors (observed group) and 30 normal gastric samples. The clinical pathological data was statistically analyzed by chi-square methods.
Results: The positive rate of CXCR4 and CD133 expression in the observed group was 94.44 (85/90) and 95.55 (86/90) respectively. The expression of CXCR4 and CD133 were correlated with age and gender of patients, and position, size, & depth of the tumor, lymphatic invasion and node metastasis (p < 0.05). While CXCR4 was positive, CD133 had a positive rate of 92.22% but the positive rate was 2.22% when CXCR4 expression was negative (χ2 = 58.657; p < 0.001).
Conclusion: Overall this data suggests that increased expression of CXCR4 and CD133 might be attributed with disease progression and malignant transformation of gastric epithelium cells. A significant correlation was found in between CXCR4 and CD133 expression and their co-expression may play significant role in invasiveness of gastric cancer.
Stein JV, Nombela-Arrieta C. Chemokine control of lymphocyte trafficking: a general overview. Immunology 2005; 116:1-12.
Wang B, Wang W, Niu W, et al. SDF-1/CXCR4 axis promotes directional migration of colorectal cancer cells through up regulation of integrin αvβ6. Carcinogenesis 2014; 35:282-91.
Takabatake Y, Sugiyama T, Kohara H, et al. The CXCL12 (SDF-1)/CXCR4 axis is essential for the development of renal vasculature. J Am Soc Nephrol 2009;20:1714-23.
Dommange F, Cartron G, Espanel C, et al. CXCL12 polymorphism and malignant cell dissemination/tissue infiltration in acute myeloid leukemia. FASEB J 2006; 20:1913-5.
Koshiba T, Hosotani R, Miyamoto Y, et al. Expression of stromal cell-derived factor 1 and CXCR4 ligand receptor system in pancreatic cancer: apossible role for tumor progression. Clin Cancer Res 2000;6:3530-5.
Yin AH, Miraglia S, Zanjani ED, et al. AC133, a novel marker for human hematopoietic stem and progenitor cells. Blood 1997;90:5002-12.
Choi SA, Wang KC, Phi JH, et al. A distinct subpopulation within CD133 positive brain tumor cells shares characteristics withendothelial progenitor cells. Cancer Lett 2012;324:221-30.
Li Z. CD133: a stem cell biomarker and beyond. Exp Hematol Oncol 2013;2:17.
Yanagisawa S, Kadouchi I, Yokomori K, et al. Identification and metastatic potential of tumor -initiating cells in malignant rhabdoid tumor of the kidney. Clin Cancer Res 2009; 15:3014-22.
Hermann PC, Huber SL, Herrler T, et al. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer. Cell Stem Cell 2007; 1:313-23.
D’Alterio C, Consales C, Polimeno MN, et al. Concomitant CXCR4 and CXCR7 expression predicts poor prognosis in renal cancer. Curr Cancer Drug Targets 2010; 10:772-81.
Dubrovska A, Hartung A, Bouchez LC, et al. CXCR4 activation maintains a stem cell population in tamoxifen-resistant breast cancer cells through AhRsignalling. Br J Cancer 2012; 107:43-52.
Miki J, Furusato B, Li H, et al. Identification of putative stem cell markers: CD133 and CXCR4, in hTERT-immortalized primary nonmalignant and malignant tumor-derived human prostate epithelial cell lines and in prostate cancer specimens. Cancer Res 2007; 67:3153-61.
Satoshi I, Toru Y, Jianglin F, Ryohei K. Expression of CXCR4 and its ligand SDF-1 in intestinal-type gastric cancer is associated with lymph node and liver metastasis. Anticancer Res 2009; 29: 4751-4758.
Shibuta K, Mori M, Shimoda K, et al. Regional expression of CXCL12/CXCR4 in liver and hepatocellular carcinoma and cell-cycle variation during in vitro differentiation. Jpn J Cancer Res 2002;93:789-97.
D'Alterio C, Cindolo L, Portella L, et al. Differential role of CD133 and CXCR4 in renal cell carcinoma. Cell Cycle 2010;9:4492-500.
Suetsugu A, Nagaki M, Aoki H, et al. Characterization of CD133+ hepatocellular carcinoma cells as cancer stem/progenitor cells. BiochemBiophys Res Commun 2006; 351:820-4.
Yu JW, Zhang P, Wu JG, et al. Expressions and clinical significances of CD133 protein and CD133 mRNA in primarylesion of gastric adenocacinoma. J ExpClin Cancer Res 2010;29:141.
Horst D, Kriegl L, Engel J, et al. CD133 expression is an independent prognostic marker for low survival in colorectal cancer. Br J Cancer 2008; 99:1285-9.
Chao C, Carmical JR, Ives KL, et al. CD133+ colon cancer cells are more interactive with the tumor microenvironment than CD133- cells. Lab Invest 2012; 92:420-36.
Shan-shan Z, Zhi-peng H, Ying-ying J, et al. CD133+CXCR4+ colon cancer cells exhibit metastatic potential and predict poor prognosis of patients. BMC Med 2012; 10:85.
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