Expression pattern of CXC chemokine receptor-4 is correlated with lymph node metastasis in human invasive ductal carcinoma

Kato, Masahiro; Kitayama, Joji; Kazama, Shinsuke; Nagawa, Hirokazu

doi:10.1186/bcr627

Cited by 242 publications

(208 citation statements)

References 30 publications

(29 reference statements)

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“…Although immunohistochemical studies in HNSCC, melanoma, and breast cancer have suggested a role for CXCR4 in lymph node metastasis, our examination found no correlation between CXCR4 expression and metastasis either in differentiating N þ from NÀ or N þ from lymph node metastasis (Robledo et al, 2001;Kato et al, 2003;Uchida et al, 2003;Delilbasi et al, 2004). Experiments in mice which inserted CXCR4 into metastatic cells resulted in an increase in hematogenous metastasis only, and blockade of CXCR4/SDF-1 interaction has a much greater inhibitory effect on hematogenous than lymphatic metastasis (Muller et al, 2001;Murakami et al, 2002).…”

Section: Discussioncontrasting

confidence: 81%

Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity

et al. 2004

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Metastasis via the lymphatics is a major risk factor in squamous cell carcinoma of the oral cavity (OSCC). We sought to determine whether the presence of metastasis in the regional lymph node could be predicted by a gene expression signature of the primary tumor. A total of 18 OSCCs were characterized for gene expression by hybridizing RNA to Affymetrix U133A gene chips. Genes with differential expression were identified using a permutation technique and verified by quantitative RT-PCR and immunohistochemistry. A predictive rule was built using a support vector machine, and the accuracy of the rule was evaluated using crossvalidation on the original data set and prediction of an independent set of four patients. Metastatic primary tumors could be differentiated from nonmetastatic primary tumors by a signature gene set of 116 genes. This signature gene set correctly predicted the four independent patients as well as associating five lymph node metastases from the original patient set with the metastatic primary tumor group. We concluded that lymph node metastasis could be predicted by gene expression profiles of primary oral cavity squamous cell carcinomas. The presence of a gene expression signature for lymph node metastasis indicates that clinical testing to assess risk for lymph node metastasis should be possible.

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Section: Discussioncontrasting

confidence: 81%

Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity

et al. 2004

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“…A growing number of studies have confirmed that CXCR4 is expressed on the surface of a variety of tumor cells (such as salivary adenoid cystic carcinoma, breast cancer, and oral squamous carcinoma cells). It interacts with its corresponding chemokines, including CXCL12, and the molecular pair then influences the biological behavior of tumor cells (Muller et al, 2006;Kato et al, 2003;Almofti et al, 2004). We found here that, although pancreatic cancer cells do not themselves express CXCL12, they do express CXCR4 which was confirmed by immunoblotting mehhod (Grzesiak et al 2007); therefore, these cells are capable of responding to chemotactic signals from CXCL12.…”

Section: Discussionsupporting

confidence: 56%

CXCL12-CXCR4 Promotes Proliferation and Invasion of Pancreatic Cancer Cells

Shen

Zheng²,

Lu³

et al. 2013

Asian Pacific Journal of Cancer Prevention

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Objective: CXCL12 exerts a wide variety of chemotactic effects on cells. Evidence indicates that CXCL12, in conjunction with its receptor, CXCR4, promotes invasion and metastasis of tumor cells. Our objective was to explore whether the CXCL12-CXCR4 biological axis might influence biological behavior of pancreatic cancer cells. Methods: Miapaca-2 human pancreatic cancer cells were cultured under three different conditions: normal medium (control), medium + recombinant CXCL12 (CXCL12 group), or medium + CXCR4-inhibitor AMD3100 (AMD3100 group). RT-PCR was applied to detect mRNA expression levels of CXCL12, CXCR4, matrix metalloproteinase 2 (MMP-2), MMP-9, and human urokinase plasminogen activator (uPA). Additionally, cell proliferation and invasion were performed using CCK-8 colorimetry and transwell invasion assays, respectively. Results: CXCL12 was not expressed in Miapaca-2 cells, but CXCR4 was detected, indicating that these cells are capable of receiving signals from CXCL12. Expression of extracellular matrix-degrading enzymes MMP-2, MMP-9, and uPA was upregulated in cells exposed to exogenous CXCL12 (P<0.05). Additionally, both proliferation and invasion of pancreatic cancer cells were enhanced in the presence of exogenous CXCL12, but AMD3100 intervention effectively inhibited these processes (P<0.05). Conclusions: The CXCL12-CXCR4 biological axis plays an important role in promoting proliferation and invasion of pancreatic cancer cells.

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“…Nuclear staining has also been described in breast cancer. 17 The significance of the role of CXCR4 will have to be determined in a large cohort of bladder tumor patients undergoing long-term observation for disease outcome. Only such a study will help determine the prognostic value of CXCR4 mRNA and protein expression.…”

Section: Discussionmentioning

confidence: 99%

“…Antigen retrieval was performed using citrate buffer (Antigen Retrieval Citra; BioGenex, San Ramon, CA, USA) and the microwave method. 17 Nonspecific binding sites were blocked with 2% normal goat serum in PBS. The TMA was incubated with mouse anti-human CXCR4 monoclonal antibody (Clone 12G5; R&D Systems) for 1 hr at room temperature at a dilution of 1:500.…”

Section: Immunohistochemistrymentioning

confidence: 99%

CXCR4 expression reflects tumor progression and regulates motility of bladder cancer cells

Retz

Sidhu

Blaveri

et al. 2004

Intl Journal of Cancer

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Transitional cell carcinoma of the urinary bladder remains life threatening due to the high occurrence of metastases. Emerging evidence suggests that chemokines and their receptors play a critical role in tumor metastases. In our study, we performed a systematic analysis of the mRNA and protein expression levels of all 18 chemokine receptors in normal urothelium and bladder cancer. CXCR4 was the only chemokine receptor whose mRNA expression level was upregulated in bladder cancer cell lines as well as in invasive and locally advanced bladder cancer tissue samples (pT2-pT4). In contrast, superficial bladder tumors (pTa and pT1) displayed low CXCR4 expression levels and normal urothelial cells were negative for CXCR4. Immunohistochemistry of a bladder cancer tissue microarray (TMA) confirmed that a subgroup of invasive bladder cancers revealed a high CXCR4 protein expression, while superficial bladder tumors showed low immunoreactivity. To investigate the functional significance of CXCR4 expression, we performed migration and invasion assays. Exposure of CXCR4-positive bladder cancer cells to CXCL12 in a Boyden chamber type assay provoked a significant increase in migration as well as invasion across a Matrigel barrier. Enhanced migration and invasion were inhibited by a CXCR4-specific blocking antibody. In contrast, normal urothelial cells did not respond to CXCL12 and lacked chemotactic migration. In conclusion, bladder cancer cells express CXCR4 progressively with advanced tumorigenesis and this receptor interacts with CXCL12 to mediate tumor chemotaxis and invasion through connective tissue. These properties identify CXCR4 as a potential target for the attenuation of bladder cancer metastases. © 2004 Wiley-Liss, Inc.Key words: chemokine; bladder cancer; metastasis; migration; invasion Transitional cell carcinoma of the bladder is the most frequent tumor of the urinary tract. Despite advances in early detection and therapy, bladder cancer remains life threatening due to the high occurrence of metastases. Radical cystectomy is the preferred treatment for muscle-invasive bladder cancer in the United States, Japan and some countries of Europe. However, at least 50% of patients with locally advanced disease are expected to develop systemic progression within 3 years. 1 Patients suffering from metastatic bladder cancer are commonly treated with systemic chemotherapy. Analyzing survival rates from standard chemotherapy schedules such as M-VAC (methotrexate, vinblastine, adriamycin and cisplatin), results are more or less discouraging. In the Loehrer trial, only 5 of 133 (3.7%) of the patients randomized to M-VAC were alive at the 6-year follow-up time. These results indicate that patients with systemic metastases continue to be incurable by chemotherapy. 2,3 Despite the fact that it is the metastases rather than the primary tumors that cause most cancer deaths, there has been little progress in identifying drugs to specifically block metastases.Metastasis is not a simple phenomenon, but a highly organized process com...

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Expression pattern of CXC chemokine receptor-4 is correlated with lymph node metastasis in human invasive ductal carcinoma

Cited by 242 publications

References 30 publications

Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity

Gene expression signature predicts lymphatic metastasis in squamous cell carcinoma of the oral cavity

CXCL12-CXCR4 Promotes Proliferation and Invasion of Pancreatic Cancer Cells

CXCR4 expression reflects tumor progression and regulates motility of bladder cancer cells

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