Study on the Relationship Between CXCR4 Expression and Perineural Invasion in Pancreatic Cancer

  • Jiang, Yu-Mei (Key Laboratory of Food Nutrition and Safety Ministry of Education, Tianjin University of Science and Technology, Tianjin International Joint Academy of Biomedicine) ;
  • Li, Guang (Department of Biology, Tianjin Medical University) ;
  • Sun, Bao-Cun (Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University) ;
  • Zhao, Xiu-Lan (Department of Pathology, Tianjin Cancer Hospital, Tianjin Medical University) ;
  • Zhou, Zhong-Kai (Key Laboratory of Food Nutrition and Safety Ministry of Education, Tianjin University of Science and Technology, Tianjin International Joint Academy of Biomedicine)
  • Published : 2014.06.30


Background: Recent reports have shown that C-X-C chemokine receptor 4 (CXCR4) plays an important role in metastasis. Despite a clear understanding of the protein's structure and properties, its functional role remains elusive. We conducted the present study to evaluate the expressions of CXCR4 in pancreatic cancer, and to investigate its relationship with clinicopathological parameters, especially perineural invasion(PNI). Materials and Methods: The association between CXCR4 expression and perineural invasion was determined by immunohistochemistry in pancreatic cancer patients (n=51). Results: CXCR4 expression was correlated with the existence of PNI and the type of PNI (p=0.042, p=0.040). TIMP-2 expression was also correlated with the existence, the pathway and degree of PNI (p=0.000, p=0.006, p=0.000). Conclusions: Our results suggest an association between PNI and expression of CXCR4 and TIMP-2 in pancreatic cancer. CXCR4 may promote the occurrence of PNI in pancreatic cancer cells by decreasing the inhibition of TIMPs on MMP.


  1. Zhang S, Qi L, Li M, et al (2008). Chemokine CXCL12 and its receptor CXCR4 expression are associated with perineural invasion of prostate cancer. J Exp Clin Cancer Res, 27, 62.
  2. Stumm R, Hollt V (2007). CXC chemokine receptor 4 regulates neuronal migration and axonal pathfinding in the developing nervous system: implications for neuronal regeneration in the adult brain. J Mol Endocrinol, 38, 377-82.
  3. Tang CH, Tan TW, Fu WM, Yang RS (2008) Involvement of matrix metalloproteinase-9 in stromal cell-derived factor-1/CXCR4 pathway of lung cancer metastasis. Carcinogenesis, 29, 35-43.
  4. Zhang JF, Hua R, Sun YW, et al (2013). Influence of perineural invasion on survival and recurrence in patients with resected pancreatic cancer. Asian Pac J Cancer Prev, 14, 5133-9.
  5. Zhang Y, Yan Y, Dang CX (2011). Advances in mechanisms of neurotropism correlated to perineural invasion in pancreatic cancer. Chin J Bases Clin General Surg, 18, 21-5.
  6. Loetscher M, Geiser T, O'Reilly T, et al (1994). Cloning of a human seven-transmembrane domain receptor, LESTR, that is highly expressed in leukocytes. J Biol Chem, 269, 232-7.
  7. Ayala GE, Wheeler TM, Shine HD, et al (2001). In vitro dorsal root ganglia and human prostate cell line interaction: redefining perineural invasion in prostate cancer. Prostate, 49, 213-23.
  8. Chen WQ, Liang D, Zhang SW, et al (2013). Pancreatic cancer incidence and mortality patterns in China, 2009. Asian Pac J Cancer Prev, 14, 7321-4.
  9. Lowenfels AB, Maisonneuve P (2004). Epidemiology and prevention of pancreatic cancer. Jpn J Clin Oncol, 34, 238-44.
  10. Ma J, Jiang Y, Jiang Y, et al (2008). Expression of nerve growth factor and tyrosine kinase receptor A and correlation with perineural invasion in pancreatic cancer. J Gastroenterol Hepatol, 23, 1852-9.
  11. Miyazaki I (1997). Perineural invasion and surgical treatment of the pancreas head cancer, Nippon Geka Gakkai Zasshi, 98, 646-8.
  12. Pour PM, Bell RH, Batra SK (2003). Neural invasion in the staging of pancreatic cancer. Pancreas, 26, 322-5.
  13. Pytliak M, Vargova V, Mechirova V (2012). Matrix metalloproteinases and their role in oncogenesis: a review. Onkologie, 35, 49-53.
  14. Richard CL, Blay J (2008). CXCR4 in Cancer and Its Regulation by PPARgamma. PPAR Res, 2008, 76941.
  15. Siegel R, Ward E, Brawley O, et al (2011). Cancer statistics, 2011: the impact of eliminating socioeconomic and racial disparities on premature cancer deaths, CA Cancer J Clin, 61, 212-36.
  16. Stumm R, Kolodziej A, Schulz S, et al (2007). Patterns of SDF-1alpha and SDF-1gamma mRNAs, migration pathways, and phenotypes of CXCR4-expressing neurons in the developing rat telencephalon. J Comp Neurol, 502, 382-99.

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