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

Ma, Xinrong; Norsworthy, Kelly J.; Kundu, Namita; Rodgers, William H.; Gimotty, Phyllis A.; Goloubeva, Olga; Lipsky, Michael; Li, Yanchun; Holt, Dawn; Fulton, Amy M.

doi:10.1158/1535-7163.mct-08-0485

Cited by 131 publications

(129 citation statements)

References 23 publications

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“…Our data establish CXCR3 and PGF as direct HIF-1 target genes in BCCs, and we have previously demonstrated that VEGFR1 is a direct HIF-1 target gene in MSCs (43). CXCR3 expression has been previously associated with decreased overall survival in breast cancer patients and shown to promote lung metastasis in mice (45).…”

Section: Discussionsupporting

confidence: 72%

Hypoxia-inducible factor–dependent breast cancer–mesenchymal stem cell bidirectional signaling promotes metastasis

Chaturvedi¹,

Gilkes²,

Wong³

et al. 2012

J. Clin. Invest.

171

163

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Metastasis involves critical interactions between cancer and stromal cells. Intratumoral hypoxia promotes metastasis through activation of hypoxia-inducible factors (HIFs). We demonstrate that IntroductionAn important advance in cancer biology has been the appreciation that, in addition to somatic mutations in oncogenes and tumor suppressor genes within cancer cells, a major mechanism driving disease progression is the interaction of cancer cells with the tumor microenvironment. The tumor stroma consists of extracellular matrix and various mesenchymal cell types, including vascular ECs and pericytes, fibroblasts, myofibroblasts, and various cells of bone marrow origin, including tumor-associated macrophages, bone marrow-derived angiogenic cells, neutrophils, mast cells, myeloid-derived suppressor cells, and mesenchymal stem cells (MSCs), which are recruited to the tumor and enhance primary tumor growth and/or promote metastasis (1). The molecular mechanisms by which stromal cells are attracted to, and communicate with, cancer cells are only understood in a limited number of contexts. For example, breast cancer cell (BCC) production of colony-stimulating factor 1 (CSF1) induces homing of CSF1 receptor-expressing tumor-associated macrophages that secrete epidermal growth factor, which binds to its receptor on cancer cells and stimulates their invasive properties (2, 3).The combination of cancer cell proliferation and stromal cell recruitment results in an imbalance between O 2 consumption and delivery. Tumor vasculature is structurally and functionally abnormal, leading to spatial and temporal heterogeneity in perfusion,

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Section: Discussionsupporting

confidence: 72%

Hypoxia-inducible factor–dependent breast cancer–mesenchymal stem cell bidirectional signaling promotes metastasis

Chaturvedi¹,

Gilkes²,

Wong³

et al. 2012

J. Clin. Invest.

171

163

View full text Add to dashboard Cite

show abstract

“…For instance, CXCR1, CXCR2 and CXCR3 in malignant melanoma [96,97]; CXCR3 in B-cell chronic lymphocytic leukemia cells [98]; CXCR5 in liver metastasis of colorectal carcinoma [99]. The CX3CR1 receptor is implicated in the perineural invasion frequently occurring in pancreatic adenocarcinoma [76] and in metastasis to bone of prostatic tumors [100].…”

Section: Tumor Cell Invasion and Migration To Distant Organsmentioning

confidence: 99%

Chemokines in cancer related inflammation

Allavena

Germano

Marchesi

et al. 2011

Experimental Cell Research

200

140

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Chemokines are key players of the cancer-related inflammation. Chemokine ligands and receptors are downstream of genetic events that cause neoplastic transformation and are abundantly expressed in chronic inflammatory conditions which predispose to cancer. Components of the chemokine system affect multiple pathways of tumor progression including: leukocyte recruitment, neo-angiogenesis, tumor cell proliferation and survival, invasion and metastasis.Evidence in pre-clinical and clinical settings suggests that the chemokine system represents a valuable target for the development of innovative therapeutic strategies

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“…Besides their functions in the immune system, chemokines and chemokine receptors also play a critical role in tumor initiation, progression, and metastasis (4 -6). Recent studies clearly suggest that in several malignancies, tumor cells express different chemokines and their receptors that are associated with more aggressive disease and poorer prognosis (7)(8)(9)(10)(11)(12).…”

mentioning

confidence: 99%

CXCR3-B Can Mediate Growth-inhibitory Signals in Human Renal Cancer Cells by Down-regulating the Expression of Heme Oxygenase-1

Datta

Banerjee

Gasser

et al. 2010

Journal of Biological Chemistry

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The chemokine receptor CXCR3 may play a critical role in the growth and metastasis of tumor cells, including renal tumors. It has been shown that CXCR3 has two splice variants with completely opposite functions; CXCR3-A promotes cell proliferation, whereas CXCR3-B inhibits cell growth. We recently demonstrated that the expression of growth-promoting CXCR3-A is up-regulated, and the growth-inhibitory CXCR3-B is markedly down-regulated in human renal cancer tissues; and the overexpression of CXCR3-B in renal cancer cells can significantly inhibit cell proliferation. However, the growth-inhibitory signal(s) through CXCR3-B are not well characterized. Here, we investigated the effector molecule(s) involved in CXCR3-B-mediated signaling events. We found that the overexpression of CXCR3-B in human renal cancer cells (Caki-1) promoted cellular apoptosis as observed by FACS analysis through Annexin-V staining. To examine whether the overexpression of CXCR3-B could alter the expression of any apoptosis-related genes in renal cancer cells, we performed a protein array. We found that CXCR3-B overexpression significantly down-regulated the expression of antiapoptotic heme oxygenase-1 (HO-1). By utilizing a HO-1 promoter-luciferase plasmid, we showed that CXCR3-B-mediated down-regulation of HO-1 was controlled at the transcriptional level as observed by luciferase assay. We also demonstrated that the inhibition of HO-1 expression using siRNA promoted apoptosis of renal cancer cells. Finally, we observed that human renal cancer tissues expressing low amounts of CXCR3-B significantly overexpress HO-1 at both mRNA and protein level. Together, we suggest that the overexpression of CXCR3-B may prevent the growth of renal tumors through the inhibition of antiapoptotic HO-1.

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

Cited by 131 publications

References 23 publications

Hypoxia-inducible factor–dependent breast cancer–mesenchymal stem cell bidirectional signaling promotes metastasis

Hypoxia-inducible factor–dependent breast cancer–mesenchymal stem cell bidirectional signaling promotes metastasis

Chemokines in cancer related inflammation

CXCR3-B Can Mediate Growth-inhibitory Signals in Human Renal Cancer Cells by Down-regulating the Expression of Heme Oxygenase-1

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