High Chemokine Receptor CXCR4 Level in Triple Negative Breast Cancer Specimens Predicts Poor Clinical Outcome

Chu, Quyen D.; Panu, Lori; Holm, Neal; Li, Benjamin D.L.; Johnson, Lester W.; Zhang, Songlin

doi:10.1016/j.jss.2008.09.020

Cited by 86 publications

(67 citation statements)

References 23 publications

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“…Some reports also indicated that they are essential for transendothelial cancer cell migration as well as vascular permeability (Krohn et al 2009;Lin et al 2009;Pradelli et al 2009;Wang et al 2009;Deutsch et al 2008;Varney et al 2006). Overexpression of these chemokine receptors in cancer specimens predicts a worse outcome in patients with cancer (Xiang et al 2009;Chu et al 2010).…”

Section: Discussionmentioning

confidence: 99%

Comparative Analysis of Chemokine Receptor's Expression in Mesenchymal Stem Cells Derived from Human Bone Marrow and Adipose Tissue

et al. 2010

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Mesenchymal stem cells (MSCs) are considered as promising candidates for new clinical trials of cell therapies. Bone marrow (BM) was the first source reported to contain MSCs; however, using it may be detrimental due to the highly invasive aspiration procedures. More recently, adipose tissue, attainable by a less invasive method, has been introduced as an alternative source of MSCs. So far, MSCs derived from these two sources have been compared in different characters; however, one of the main properties, i.e., the expression of chemokine receptors, has been ignored in these comparisons. In the present study, human MSCs were derived from bone marrow and adipose tissues and characterized by their expression of some cell surface antigens and also differentiation capacity. The expression of five selected chemokine receptors, which seems to be important in cell homing, was also compared. Semiquantitative reverse transcription-polymerase chain reaction method was used to assess gene expression levels of these chemokine receptors. Our results indicate that expression of these receptors in human MSCs, derived from adipose tissue, was higher than MSCs from bone marrow. Chemokine receptors and their ligands and adhesion molecules play an important role in tissue-specific homing of leukocytes and have also been implicated in trafficking of hematopoietic precursors into and through tissues. Therefore, MSCs from adipose tissue may show a better migration and homing capacity and they might be a better candidate for therapeutic purposes.

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Section: Discussionmentioning

confidence: 99%

Comparative Analysis of Chemokine Receptor's Expression in Mesenchymal Stem Cells Derived from Human Bone Marrow and Adipose Tissue

et al. 2010

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“…In addition, cytokines such as SDF-1 (also known as CXCL12) produced by breast carcinoma-associated fibroblasts (but not normal fibroblasts) may promote proliferation of tumor cells, which express the SDF-1 receptor CXCR4 (39). The level of expression of SDF-1 in serum has been associated with poor survival in breast cancer patients (40,41). Other growth factors such as HGF, produced by mammary stromal cells, may also have a profound effect…”

Section: Cellular Components Of the Tumor Microenvironmentmentioning

confidence: 99%

Breast cancer stem cells, cytokine networks, and the tumor microenvironment

Korkaya¹,

Liu²,

2011

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Many tumors, including breast cancer, are maintained by a subpopulation of cells that display stem cell properties, mediate metastasis, and contribute to treatment resistance. These cancer stem cells (CSCs) are regulated by complex interactions with the components of the tumor microenvironment -including mesenchymal stem cells, adipocytes, tumor associated fibroblasts, endothelial cells, and immune cells -through networks of cytokines and growth factors. Since these components have a direct influence on CSC properties, they represent attractive targets for therapeutic development.

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“…Overexpression of CXCR4 in primary breast tumors is related to an aggressive phenotype and lymph-node metastases (2)(3)(4). Similarly, elevated CXCR4 expression in estrogen (ER) and progestin receptor (PR)-negative breast cancers, as well as ER2 − /PR2 − /HER-2 − triple-negative breast cancers, is closely associated with lymph-node metastasis and poor prognosis (5,6). Binding of CXCL12 to CXCR4 promotes tumor progression by several mechanisms associated with the activation of a number of signaling pathways required for biological responses, including chemotaxis (7).…”

mentioning

confidence: 99%

Targeting CXCL12/CXCR4 signaling with oncolytic virotherapy disrupts tumor vasculature and inhibits breast cancer metastases

Gil¹,

Seshadri

Komorowski³

et al. 2013

Proc. Natl. Acad. Sci. U.S.A.

133

128

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Oncolytic viruses hold promise for the treatment of cancer, but their interaction with the tumor microenvironment needs to be elucidated for optimal tumor cell killing. Because the CXCR4 receptor for the stromal cell-derived factor-1 (SDF-1/CXCL12) chemokine is one of the key stimuli involved in signaling interactions between tumor cells and their stromal microenvironment, we used oncolytic virotherapy with a CXCR4 antagonist to target the CXCL12/CXCR4 signaling axis in a triple-negative 4T1 breast carcinoma in syngeneic mice. We show here that CXCR4 antagonist expression from an oncolytic vaccinia virus delivered intravenously to mice with orthotopic tumors attains higher intratumoral concentration than its soluble counterpart and exhibits increased efficacy over that mediated by oncolysis alone. A systemic delivery of the armed virus after resection of the primary tumor was efficacious in inhibiting the development of spontaneous metastasis and increased overall tumor-free survival. Inhibition of tumor growth with the armed virus was associated with destruction of tumor vasculature, reductions in expression of CXCL12 and VEGF, and decrease in intratumoral numbers of bone marrow-derived endothelial and myeloid cells. These changes led to induction of antitumor antibody responses and resistance to tumor rechallenge. Engineering an oncolytic virus armed with a CXCR4 antagonist represents an innovative strategy that targets multiple elements within the tumor microenvironment. As such, this approach could have a significant therapeutic impact against primary and metastatic breast cancer. viral oncotherapy | vascular targeting

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High Chemokine Receptor CXCR4 Level in Triple Negative Breast Cancer Specimens Predicts Poor Clinical Outcome

Cited by 86 publications

References 23 publications

Comparative Analysis of Chemokine Receptor's Expression in Mesenchymal Stem Cells Derived from Human Bone Marrow and Adipose Tissue

Comparative Analysis of Chemokine Receptor's Expression in Mesenchymal Stem Cells Derived from Human Bone Marrow and Adipose Tissue

Breast cancer stem cells, cytokine networks, and the tumor microenvironment

Targeting CXCL12/CXCR4 signaling with oncolytic virotherapy disrupts tumor vasculature and inhibits breast cancer metastases

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