Differential Functional Activation of Chemokine Receptor CXCR4 Is Mediated by G Proteins in Breast Cancer Cells

Holland, Jane D.; Kochetkova, Marina; Akekawatchai, Chareeporn; Dottore, Mara; Lopez, Angel F.; McColl, Shaun R.

doi:10.1158/0008-5472.can-05-1631

Cited by 101 publications

(99 citation statements)

References 39 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…1b. Even though overexpression of CXCR4 in MCF10A cell line has been reported before [26], we could not find in the literature any particular data explaining why the levels of CXCR4 were higher in non-cancerous than in cancerous cells. Moreover, there are no published data about the expression change of CXCR4 in those cell lines with time.…”

Section: Discussioncontrasting

confidence: 80%

Changes in gene expression of CXCR4, CCR7 and BCL2 after treatment of breast cancer cells with saponin extract from Tribulus terrestris

Goranova¹,

Ss²,

Vs³

et al. 2015

neo

View full text Add to dashboard Cite

Saponins are natural substances produced by a large number of plants, one of which is Tribulus terrestris L. (TT). They have been reported to possess an antitumor activity exerted by regulating various signaling pathways in the cell. Although the mechanisms of action of saponin extracts from various plants have been widely studied, limited data are available about TT. The present study aimed to analyze the impact of saponin extract from TT on cell processes in breast carcinoma cell lines. The variations in expression of a group of 32 selected genes were examined by real-time PCR after saponin treatment of MCF7 and MCF10A cell lines. Only three genes -CXCR4, CCR7 and BCL2, showed changes in their mRNA levels after the application of the herb extract. While CXCR4 expression was reduced in both cell lines, CCR7 and BCL2 levels decreased only in tumorigenic MCF7 cells, implying cell-specificity of the saponin action. Our results suggested that TT extract containing saponins was likely to affect the processes of apoptosis and metastasizing of cancer cells. Further in vivo studies will show its applicability as an anticancer therapeutic agent.

show abstract

Section: Discussioncontrasting

confidence: 80%

Changes in gene expression of CXCR4, CCR7 and BCL2 after treatment of breast cancer cells with saponin extract from Tribulus terrestris

Goranova¹,

Ss²,

Vs³

et al. 2015

neo

View full text Add to dashboard Cite

show abstract

“…3 Blocking the interaction between CXCR4 and its ligand CXCL12, dramatically reduces breast and other cancer metastases in mouse models. 4 Our recent results have also provided a direct correlation between functional activation of CXCR4 and CCR7 and the invasive, metastatic phenotype of breast cancer cells 5 further supporting a highly important role for these molecules in tumor dissemination to distant sites. Initial studies suggested that these surface molecules induce directional migration of malignant cells along chemokine gradients towards secondary tumor sites in a manner that is similar to the process of lymphocyte homing.…”

mentioning

confidence: 54%

“…We found that ligands for both CXCR4 and CCR7 decreased anoikis only in highly invasive, metastatic breast cancer cells but failed to affect apoptosis in untransformed or non-metastatic cells with silent CXCR4 and CCR7. 5 Thus detachment-induced cell death in non-invasive MDA-453 (Figure 2a), MDA-134 and MCF-10A (not shown) cells was not affected by incubation with chemokines and was only reduced by the addition of serum. The selectivity of anoikisreducing function of CXCL12 and CCL21 was further documented by the inability of these chemokines to induce cytotoxic drug resistance.…”

Section: Resultsmentioning

confidence: 83%

See 1 more Smart Citation

Chemokine receptors CXCR4 and CCR7 promote metastasis by preventing anoikis in cancer cells

2009

View full text Add to dashboard Cite

Chemokine receptors are essential mediators of the metastatic spread in various cancer types; however their precise function in the development of secondary tumors remains poorly understood. We report here a novel property of the chemokine receptors CXCR4 and CCR7 in inhibiting detachment-induced cell death -anoikis, which is believed to be one of the major blocks in the metastatic spread of various neoplasms. Activation of these chemokine receptors by their respective ligands, CXCL12 and CCL21 specifically reduced the sensitivity of metastatic breast cancer cells to anoikis by a distinct mechanism of selective regulation of pro-apoptotic Bmf and anti-apoptotic Bcl-xL proteins. Consequently, functional CXCR4 and CCR7 increased cell survival in the absence of correct ECM attachment both in vitro and in vivo. We also demonstrated that preventing chemokineinduced reduction in Bmf levels significantly attenuated breast cancer metastasis in an experimental mouse model. These results provide evidence for a previously unknown axis in malignant tumors, which connects chemokine receptors with deregulated apoptosis in the absence of the appropriate cell -ECM interaction and may offer novel targets for therapeutic intervention for the treatment of metastatic breast and potentially other tumors. Cell Death and Differentiation (2009) 16, 664-673; doi:10.1038/cdd.2008; published online 9 January 2009The main cause of cancer-related deaths is the spread of tumor cells to sites distant from the primary locus and the subsequent establishment of secondary lesions. The heterogeneity and complexity of malignant transformation make it difficult to identify common molecular mechanisms governing the metastatic progression of cancer and potentially account for the lack of effective treatments for malignant cancers. Recently, members of the chemokine receptor family of G-protein-coupled receptors (GPCRs) have been assigned a major role in this process (reviewed in Zlotnik 1 ). It is becoming increasingly clear that many members of this family regulate a complex milieu of interactions between tumor cells, stromal cells, tumor infiltrating leukocytes and endothelial cells and that better understanding of the specific actions of chemokines and their receptors in promoting malignancy will significantly contribute to combating cancer. 2 CXCR4 and CCR7 are the major chemokine receptors found on a wide range of tumor cells and high levels of these receptors are associated with higher grade and poor prognosis of breast, lung, colon and other cancers. 3 Blocking the interaction between CXCR4 and its ligand CXCL12, dramatically reduces breast and other cancer metastases in mouse models. 4 Our recent results have also provided a direct correlation between functional activation of CXCR4 and CCR7 and the invasive, metastatic phenotype of breast cancer cells 5 further supporting a highly important role for these molecules in tumor dissemination to distant sites. Initial studies suggested that these surface molecules induce directional migration of ma...

show abstract

“…Loss of E-cadherin expression has been shown to correlate with invasion and metastasis in many types of carcinoma [49]. Madhavan et al [50] reported that the expression of Ecadherin and P-cadherin showed significant down-regulation in node-positive tumours compared to node-negative tumours when examined by IHC in 51 cases of breast cancer that included 29 node-negative and 22 node-positive cases.…”

Section: Diagnostic/prognostic Markersmentioning

confidence: 99%

Membrane and membrane‐associated proteins involved in the aggressive phenotype displayed by highly invasive cancer cells

2008

View full text Add to dashboard Cite

Invasion, the penetration of tumour cells into adjacent tissues, is a fundamental characteristic of malignant carcinomas and a first step in the metastatic process. The molecular mechanisms involved in tumour cell invasion are complex, but over the last couple of decades the knowledge base has grown quite considerably and many proteins with important roles in invasion have been identified and characterised. Benign tumours typically are encapsulated, which inhibits their ability to behave in a malignant manner, meaning these tumours do not grow in a location-limited less aggressive manner, do not invade surrounding tissues and do not metastasise. The ability of malignant tumours to invade and metastasise is the major cause of death for cancer patients. A greater insight into the molecular basis of cancer invasion and metastasis will lead to the development of novel therapies and specific panels of biomarkers for use in the treatment and diagnosis/monitoring in many types of metastatic cancer.

show abstract

Differential Functional Activation of Chemokine Receptor CXCR4 Is Mediated by G Proteins in Breast Cancer Cells

Cited by 101 publications

References 39 publications

Changes in gene expression of CXCR4, CCR7 and BCL2 after treatment of breast cancer cells with saponin extract from Tribulus terrestris

Changes in gene expression of CXCR4, CCR7 and BCL2 after treatment of breast cancer cells with saponin extract from Tribulus terrestris

Chemokine receptors CXCR4 and CCR7 promote metastasis by preventing anoikis in cancer cells

Membrane and membrane‐associated proteins involved in the aggressive phenotype displayed by highly invasive cancer cells

Contact Info

Product

Resources

About