Downregulation of CXCR7 inhibits proliferative capacity and stem cell-like properties in breast cancer stem cells

Tang, Xin; Li, Xiang; Li, Zitao; Liu, Yunshuang; Yao, Lihong; Song, Shuang; Yang, Hongyan; Li, Caijuan

doi:10.1007/s13277-016-5180-1

Cited by 23 publications

(12 citation statements)

References 32 publications

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“…3, these cells expressed relatively high levels of CXCR4 and CXCR7 compared to NMVP and HMVP1 cells. In further support of this hypothesis, Dubrovska et al reported that in human PCa cell lines (DU145 and PC3), CXCR4 expression was elevated in the CD44 + /CD133 + subpopulation of cells and that these cells were considerably more tumorigenic [57] and recent evidence suggests that CXCR7 is involved in maintaining the stem like properties of breast, glioblastoma and lung cancer cells [58–60]. …”

Section: Discussionmentioning

confidence: 99%

Proinflammatory CXCL12–CXCR4/CXCR7 Signaling Axis Drives Myc-Induced Prostate Cancer in Obese Mice

et al. 2017

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Obesity is a prognostic risk factor in the progression of prostate cancer (PCa), however, the molecular mechanisms involved are unclear. In this study, we provide preclinical proof of concept for the role of a pro-inflammatory CXCL12-CXCR4/CXCR7 signaling axis in an obesity-driven mouse model of HiMyc prostate cancer. Analysis of the stromal vascular fraction (SVF) from periprostatic white adipose tissue (ppWAT) from obese HiMyc mice at 6 months of age revealed a dramatic increase in mRNAs encoding various chemokines, cytokines, growth factors and angiogenesis mediators, with CXCL12 among the most significantly upregulated genes. Immunofluorescence staining of ventral prostate tissue from obese HiMyc mice revealed high levels of CXCL12 in the stromal compartment as well as high staining for CXCR4 and CXCR7 in the epithelial compartment of tumors. PCa cell lines derived from HiMyc tumors (HMVP2 and derivative cell lines) displayed increased protein expression of both CXCR4 and CXCR7 compared to protein lysates from a non-tumorigenic prostate epithelial cell line (NMVP cells). CXCL12 treatment stimulated migration and invasion of HMVP2 cells but not NMVP cells. These effects of CXCL12 on HMVP2 cells were inhibited by the CXCR4 antagonist AMD3100 as well as knockdown of either CXCR4 or CXCR7. CXCL12 treatment also produced rapid activation of STAT3, NFkB, and MAPK signaling in HMVP2 cells which was again attenuated by either AMD3100 or knockdown of CXCR4 or CXCR7. Collectively, these data suggest that CXCL12 secreted by stromal cells activates invasiveness of PCa cells and may play a role in driving tumor progression in obesity. Targeting the CXCL12-CXCR4/CXCR7 axis could lead to novel approaches for offsetting the effects of obesity on PCa progression.

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Section: Discussionmentioning

confidence: 99%

Proinflammatory CXCL12–CXCR4/CXCR7 Signaling Axis Drives Myc-Induced Prostate Cancer in Obese Mice

et al. 2017

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“…An important driver of chemokine gradients in the tumor microenvironment are cancer cells under aerobic glycolysis, which produce lactic acid that activates NF-κB and induces CXCL8 expression in vascular endothelial cells, resulting in angiogenesis in breast and colon cancer (20, 21). CXCL8 also upregulates CXCR7/ACKR3, which is involved in stemness features of cancer cells suggesting it is also likely involved in EPC mobilization (22–24).…”

Section: Introductionmentioning

confidence: 99%

Support of Tumor Endothelial Cells by Chemokine Receptors

Salazar

Zabel

2019

Front. Immunol.

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Tumor-associated vascular endothelium comprises a specialized and diverse group of endothelial cells that, although not cancer themselves, are integral to cancer progression. Targeting the tumor vasculature can have significant efficacy in reducing tumor burden, although loss of efficacy due to acquisition of resistance mechanisms is common. Here we review mechanisms by which tumor endothelial cells (TEC) utilize chemokine receptors to support tumor progression. We illustrate how chemokine receptors support and may serve as functional markers of the diverse TEC population. We focus on ACKR1 (DARC), ACKR3 (CXCR7), CXCR4, and CCR2, as these are the best studied chemokine receptors in TEC; and suggest that targeting these receptors on the tumor vasculature may prove efficacious in slowing or reversing tumor growth. We also mention CXCR2 and CXCR3 as important mediators or tumor angiogenesis, given their distinct roles with angiogenic and angiostatic chemokines, respectively.

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“…CXCR7/RDC1 receptor is expressed by immune, endothelial, and tumor cells and binds SDF-1 with high affinity [28]. Although CXCR7 was thought to act as a scavenger receptor [29], it was recently demonstrated that SDF-1/CXCR7 signaling induces CSC proliferation/survival and EMT [30, 31], supporting growth and metastasis in different tumor types.…”

Section: Introductionmentioning

confidence: 99%

PDGFR-induced autocrine SDF-1 signaling in cancer cells promotes metastasis in advanced skin carcinoma

et al. 2019

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Advanced and undifferentiated skin squamous cell carcinomas (SCCs) exhibit aggressive growth and enhanced metastasis capability, which is associated in mice with an expansion of the cancer stem-like cell (CSC) population and with changes in the regulatory mechanisms that control the proliferation and invasion of these cells. Indeed, autocrine activation of PDGFRα induces CSC invasion and promotes distant metastasis in advanced SCCs. However, the mechanisms involved in this process were unclear. Here, we show that CSCs of mouse advanced SCCs (L-CSCs) express CXCR4 and CXCR7, both receptors of SDF-1. PDGFRα signaling induces SDF-1 expression and secretion, and the autocrine activation of this pathway in L-CSCs. Autocrine SDF-1/CXCR4 signaling induces L-CSC proliferation and survival, and mediates PDGFRα-induced invasion, promoting in vivo lung metastasis. Validation of these findings in patient samples of skin SCCs shows a strong correlation between the expression of SDF1, PDGFRA, and PDGFRB, which is upregulated, along CXCR4 in tumor cells of advanced SCCs. Furthermore, PDGFR regulates SDF-1 expression and inhibition of SDF-1/CXCR4 and PDGFR pathways blocks distant metastasis of human PD/S-SCCs. Our results indicate that functional crosstalk between PDGFR/SDF-1 signaling regulates tumor cell invasion and metastasis in human and mouse advanced SCCs, and suggest that CXCR4 and/or PDGFR inhibitors could be used to block metastasis of these aggressive tumors.

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Downregulation of CXCR7 inhibits proliferative capacity and stem cell-like properties in breast cancer stem cells

Cited by 23 publications

References 32 publications

Proinflammatory CXCL12–CXCR4/CXCR7 Signaling Axis Drives Myc-Induced Prostate Cancer in Obese Mice

Proinflammatory CXCL12–CXCR4/CXCR7 Signaling Axis Drives Myc-Induced Prostate Cancer in Obese Mice

Support of Tumor Endothelial Cells by Chemokine Receptors

PDGFR-induced autocrine SDF-1 signaling in cancer cells promotes metastasis in advanced skin carcinoma

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