The expression of the chemokine receptor CXCR3 and its ligand, CXCL10, in human breast adenocarcinoma cell lines

Goldberg‐Bittman, Lilach; Neumark, Eran; Sagi‐Assif, Orit; Azenshtein, Elina; Meshel, Tsipi; Witz, Isaac P.; Ben‐Baruch, Adit

doi:10.1016/j.imlet.2003.10.020

Cited by 90 publications

(84 citation statements)

References 44 publications

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“…A trend toward larger tumor size and number of involved lymph nodes and higher CXCR3 detection was also observed. Although CXCR3 expression had been reported previously in human breast cancer cell lines (16), the current report is the first to show a relationship between CXCR3 and behavior of clinical breast cancers. Thus, this data adds to the literature that like CXCR3 expression in melanoma and colon cancer, CXCR3 is an indicator of a poor prognosis in breast cancer.…”

Section: Discussionmentioning

confidence: 48%

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CXCR3 expression is associated with poor survival in breast cancer and promotes metastasis in a murine model

Norsworthy²,

Kundu³

et al. 2009

Molecular Cancer Therapeutics

132

111

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Breast tumor cells express the chemokine receptor CXCR3, which binds the ligands CXCL9, CXCL10, and CXCL11. CXCR3 and other chemokine receptors may mediate tumor metastasis by supporting migration of tumor cells to sites of ligand expression including the lymph nodes, lungs, and bone marrow. We examined the relationship of CXCR3 expression to clinical outcome in 75 women diagnosed with early-stage breast cancer. We detected CXCR3 in malignant epithelium from all tumors. Twelve percent were weakly positive and 64% had moderate levels of CXCR3. Strong CXCR3-positive staining was observed in 24% of tumors. Kaplan-Meier survival curves showed that high CXCR3 expression was associated with poorer overall survival; the unadjusted hazard ratio was 1.56 and it was marginally significant (P = 0.07). When interactions between lymph node status and CXCR3 were considered, the adjusted hazard ratio for CXCR3 was 2.62 (P = 0.02) for women with nodenegative disease at diagnosis, whereas the hazard ratio for CXCR3 was not significant for those with node-positive disease. CXCR3 gene silencing inhibited lung colonization and spontaneous lung metastasis from mammary glandimplanted tumors in a murine model. The size or growth rate of the locally growing tumors was not affected. The antimetastatic effect of CXCR3 gene silencing was compromised in mice depleted of Natural Killer cells or with mutations in IFN-;, suggesting that the role of CXCR3 is not simply to mediate tumor cell trafficking. These studies support the continued examination of CXCR3 as a potential therapeutic target in patients with breast cancer. [Mol Cancer Ther 2009;8(3):490 -8]

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Section: Discussionmentioning

confidence: 48%

“…Considerably less is known about the role of the CXCR3 receptor, which binds the ligands CXCL9, CXCL10, and CXCL11. Human and murine breast cancer cell lines express CXCR3 mRNA and protein (3,6,16). CXCR3 has also been detected on melanoma, ovarian and renal cell carcinoma, B-cell leukemia, prostate, and colorectal cell lines (17 -22).…”

Section: Discussionmentioning

confidence: 99%

CXCR3 expression is associated with poor survival in breast cancer and promotes metastasis in a murine model

Norsworthy²,

Kundu³

et al. 2009

Molecular Cancer Therapeutics

132

111

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“…For example, CXCL9 and CXCL10 induce the migration and invasion of melanoma cell lines and multiple myeloma cells [185][186][187]. CXCR3, the receptor for CXCL9 and CXCL10 was shown to be expressed by cancer cells of solid tumors, such as breast tumor cells, renal carcinoma cells and melanoma cells [185,[188][189][190]. A direct role for CXCR3 in inducing tumor cell migration to metastatic sites was suggested by observations showing that the expression of this chemokine receptor by melanoma cells is causally involved in metastasis to lymph nodes [187].…”

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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“…Briefly, MCF7, KB, COLO205 and Jurkat (1310 4 of each) cells were plated overnight in 96-well flat bottom cell culture plates. The next day, PBMCs (1310 5 ) were added as effectors in each well and cocultured for 4 h. After incubation, the plate was centrifuged for 5 min at 1500g, and cell-free culture supernatant (100 ml) was used to measure the level of released LDH. % Cytotoxicity5(Lysis from effector-Target mixture2Lysis from effector only)2Spontaneous lysis /Maximum lysis2Spontaneous lysis3100.…”

Section: Cytotoxicity Assaymentioning

confidence: 99%

“…5,6 We have previously demonstrated that defective migration of leukocytes (T cells/NK cells) with high expression of the CXCR3B splice variant is corrected by neem leaf glycoprotein (NLGP). 7 As tumor, tumor microenvironment and tumor secreted factors dictate immune cells to subvert immune system, optimum synchronization of associated immune functions is essential to maximize tumor cell killing.…”

Section: Introductionmentioning

confidence: 99%

Restoration of dysregulated CC chemokine signaling for monocyte/macrophage chemotaxis in head and neck squamous cell carcinoma patients by neem leaf glycoprotein maximizes tumor cell cytotoxicity

et al. 2010

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Previous studies have shown that the CC chemokine receptor CCR5 is downregulated on monocyte/macrophage (MO/Mw) surfaces in head and neck squamous cell carcinoma (HNSCC) patients (stage IIIB). Ligands (RANTES, MIP-1a and MIP-1b) of this chemokine receptor were also secreted in lesser quantity from MO/Mw of HNSCC patients in comparison with healthy individuals. In an aim to restore this dysregulated receptor-ligand signaling, we have used neem leaf glycoprotein (NLGP), a novel immunomodulator reported from our laboratory. NLGP upregulated CCR5 expression, as evidenced from studies on MO/Mw of peripheral blood from HNSCC patients as well as healthy individuals. Expression of RANTES, MIP-1a and MIP-1b was also upregulated following NLGP treatment of these cells in vitro.

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The expression of the chemokine receptor CXCR3 and its ligand, CXCL10, in human breast adenocarcinoma cell lines

Cited by 90 publications

References 44 publications

CXCR3 expression is associated with poor survival in breast cancer and promotes metastasis in a murine model

CXCR3 expression is associated with poor survival in breast cancer and promotes metastasis in a murine model

Chemokines in tumor angiogenesis and metastasis

Restoration of dysregulated CC chemokine signaling for monocyte/macrophage chemotaxis in head and neck squamous cell carcinoma patients by neem leaf glycoprotein maximizes tumor cell cytotoxicity

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