Strong expression of chemokine receptor CXCR4 by pancreatic cancer correlates with advanced disease

Abstract

Certain chemokines have been proposed to distinctly contribute to tumor growth, dissemination and local immune escape. Expression of the chemokine receptor CXCR4 has been linked to tumor progression in diverse tumor entities. The aim of this study was to evaluate if the expression of CXCR4 influences progression of human pancreatic cancer. CXCR4 expression of pancreatic cancer was retrospectively assessed by immunohistochemistry in 103 patients with pancreatic cancer. Intensity of CXCR4 expression was correlated with both tumor and patient characteristics. Human pancreatic cancer revealed variable intensities of CXCR4 expression. Strong CXCR4 expression was significantly associated with advanced UICC stages (P=0.03) and revealed a trend for hematogenous metastasis (P=0.09) and progressed local tumor stages (P=0.15). In summary, strong expression of CXCR4 was significantly associated with advanced pancreatic cancer.

PAUF functions in the metastasis of human pancreatic cancer cells and upregulates CXCR4 expression

“…CXCR4-positive cancer cells migrate toward distant organs in response to a gradient of stromal cell-derived factor-1, the specific ligand of CXCR4, to form metastatic tumors. Elevated CXCR4 expression has been shown in pancreatic tumors and correlates with an advanced cancer stage and metastasis with a poor overall survival (Koshiba et al, 2000;Marchesi et al, 2004;Wehler et al, 2006;Wang et al, 2008). In line with these previous reports, our immunohistochemical results indicate CXCR4 expression in pancreatic tumor tissues.…”

Mechanisms by which CXCR4/CXCL12 cause metastatic behavior in pancreatic cancer

“…CXCR4 levels have been detected as overexpressed in pancreatic cancer tissues and exhibit a close association with the differentiation, metastasis, growth and prognosis of pancreatic cancer (8,9,20,21). The results of the present study demonstrated that the expression levels of CXCR4 in tumor tissues were increased compared with in normal tissues, indicating that CXCR4 may be involved in the development of pancreatic cancer.…”

Chemokines in tumor angiogenesis and metastasis

“…Gene array analysis of human breast cancer myoepithelial cells and myofibroblasts demonstrated up-regulation of both CXCR4 and CXCL12 which serve to enhance migration and invasion [141]. CXCR4 expression also mediates organ-specific metastasis of pancreatic cancer cells and a strong association of CXCR4 with advanced pancreatic cancer has also been suggested [142,143]. In vitro stimulation of CXCR4-positive cancer cells with CXCL12 resulted in directed migration/invasion of ovarian cancer cells [144].…”