CXCR4 Expression Increases Liver and Lung Metastasis in a Mouse Model of Pancreatic Cancer

Saur, Dieter; Seidler, Barbara; Schneider, Günter; Algül, Hana; Beck, Roswitha; Senekowitsch–Schmidtke, Reingard; Schwaiger, Markus; Schmid, Roland M.

doi:10.1053/j.gastro.2005.06.056

Cited by 171 publications

(120 citation statements)

References 41 publications

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“…A complex network of chemokine and chemokine receptors exist in tumour microenvironment. The chemokine receptor CXCR4 is one of the representative target genes (Schrader et al, 2002;Brand et al, 2005;Saur et al, 2005;Billadeau et al, 2006). In this study, we demonstrated that overall survival in the case of patients positive for CXCR4 expression was significantly lower than that in the case of patients negative for CXCR4 expression.…”

Section: Discussionmentioning

confidence: 64%

Blockade of SDF-1/CXCR4 signalling inhibits pancreatic cancer progression in vitro via inactivation of canonical Wnt pathway

et al. 2008

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Extra-pancreatic metastasis is a difficult problem for surgical intervention in pancreatic cancer. CXC chemokine receptor 4 (CXCR4) was considered to have an important role in this process. We hypothesized it may contribute to the pancreatic cancer progression through influencing canonical Wnt pathway. The purpose of this study was to examine the functional role of CXCR4 in the progression of pancreatic cancers and explore the possible mechanism. To this end, the relation between CXCR4 and clinical characteristics was analysed. shRNA against CXCR4 was applied to disrupt the SDF-1/CXCR4 signal transduction pathways in pancreatic cancer cell lines. Our results showed that overall survival in the case of patients positive for CXCR4 expression was significantly lower than that in the case of patients negative for CXCR4 expression. Notably, in vitro studies we observed that the abrogation of CXCR4 could obviously influence the pancreatic cancer cell phenotype including cell proliferation, colony formation, cell invasion and also inhibit the TOPflash activity. In addition, Wnt target genes and mesenchymal markers such as Vimentin and Slug were also inhibited in CXCR4 knockdown cells. Collectively, these data reported here demonstrate CXCR4 could modulate the canonical Wnt pathway and perhaps be a promising therapeutic target for pancreatic cancer progression.

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Section: Discussionmentioning

confidence: 64%

Blockade of SDF-1/CXCR4 signalling inhibits pancreatic cancer progression in vitro via inactivation of canonical Wnt pathway

et al. 2008

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“…Furthermore, the C-X-C chemokine receptor type 4 (CXCR4) was shown to increase liver and lung metastasis in a mouse model of pancreatic cancer (Saur et al, 2005). Together, these findings suggest a role for CXCR4 in organ-specific pancreatic cancer metastasis (Zlotnik, 2008).…”

Section: Introductionmentioning

confidence: 93%

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

et al. 2009

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Pancreatic cancer is characterized by early metastatic spread, but the process of tumor cell dissemination is largely unknown. In this study we show that the soluble protein pancreatic adenocarcinoma upregulated factor (PAUF) has an important role in the metastasis and progression of the disease. Variations in the level of PAUF, either by overexpression or knockdown, resulted in altered migration, invasion and proliferation capacity of pancreatic cancer cells. Moreover, depletion of PAUF in metastatic cells dramatically abrogated the spread of the cells to distant organs in an orthotopic xenograft mouse model. PAUF elicited the activation of the extracellular signalregulated kinase (ERK), c-Jun N-terminal kinase (JNK) and AKT intracellular signaling cascades and consequently their downstream transcription factors in an autocrine manner. Genome-wide expression analysis revealed that C-X-C chemokine receptor type 4 (CXCR4) expression was induced by PAUF overexpression but was repressed by PAUF knockdown. The PAUF-mediated increase in cancer cell motility was attenuated by the CXCR4 inhibitor, AMD3100, or by anti-CXCR4 antibody. Furthermore, immunohistochemical analysis of pancreatic tumor tissues clearly showed a significant positive correlation between PAUF and CXCR4 expression. Collectively, these findings indicate that PAUF enhances the metastatic potential of pancreatic cancer cells, at least in part, by upregulating CXCR4 expression.

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“…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].…”

Section: Chemokines and Their Receptors In Tumor Growth And Metastasismentioning

confidence: 99%

Chemokines in tumor angiogenesis and metastasis

Singh

Sadanandam

Singh

2007

Cancer Metastasis Rev

159

132

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Chemokines are a large group of low molecular weight cytokines that are known to selectively attract and activate different cell types. Although the primary function of chemokines is well recognized as leukocyte attractants, recent evidences indicate that they also play a role in number of tumor-related processes, such as growth, angiogenesis and metastasis. Chemokines activate cells through cell surface seven trans-membranes, G-protein-coupled receptors (GPCR). The role played by chemokines and their receptors in tumor pathophysiology is complex as some chemokines favor tumor growth and metastasis, while others may enhance anti-tumor immunity. These diverse functions of chemokines establish them as key mediators between the tumor cells and their microenvironment and play critical role in tumor progression and metastasis. In this review, we present some of the recent advances in chemokine research with special emphasis on its role in tumor angiogenesis and metastasis.

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CXCR4 Expression Increases Liver and Lung Metastasis in a Mouse Model of Pancreatic Cancer

Cited by 171 publications

References 41 publications

Blockade of SDF-1/CXCR4 signalling inhibits pancreatic cancer progression in vitro via inactivation of canonical Wnt pathway

Blockade of SDF-1/CXCR4 signalling inhibits pancreatic cancer progression in vitro via inactivation of canonical Wnt pathway

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

Chemokines in tumor angiogenesis and metastasis

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