Mechanisms by which CXCR4/CXCL12 cause metastatic behavior in pancreatic cancer

Zhang, Jianbo; Liu, Chengxin; Mo, Xinkai; Shi, Huan; Sheng, Li

doi:10.3892/ol.2017.7512

Cited by 35 publications

(32 citation statements)

References 30 publications

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“…This chemokine and its corresponding receptor (CXCR4) are believed to play a crucial role in many solid cancers, and are associated with metastatic spread in breast cancer, lung cancer and melanoma [40][41][42][43]. Accumulating evidence also points to a role in PDAC progression, with higher expression of CXCL12 correlating with metastasis, likely by facilitating immune evasion, and increased levels of matrix metalloproteinases leading to cellular invasion [44][45][46][47]. Within our own study, we find similar trends in the presence of other cellular populations that parallel the emergence of CXCL12-expressing iCAFs, such as a decrease in cytotoxic T cell and increase in myeloid suppressive proportions, creating the notorious immune suppressive TME well described in PDAC.…”

Section: Discussionmentioning

confidence: 99%

Single Cell Transcriptomics of Pancreatic Cancer Precursors Demonstrates Epithelial and Microenvironmental Heterogeneity as an Early Event in Neoplastic Progression

Bernard

Semaan

Huang

et al. 2018

Preprint

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Key Words: single-cell RNA sequencing, pancreatic cancer, intraductal papillary mucinous neoplasm, transcriptomic heterogeneity, precancer atlas Word Count: 3794All rights reserved. No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint . http://dx.doi.org/10.1101/306134 doi: bioRxiv preprint first posted online Apr. 26, 2018; Abstract Background: Early detection of pancreatic ductal adenocarcinoma (PDAC) remains

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Section: Discussionmentioning

confidence: 99%

Single Cell Transcriptomics of Pancreatic Cancer Precursors Demonstrates Epithelial and Microenvironmental Heterogeneity as an Early Event in Neoplastic Progression

Bernard

Semaan

Huang

et al. 2018

Preprint

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“…[16][17][18][19] Perturbation of Cxcl12 has also been associated extensively with B-cell lymphopoiesis 19 and various cancers, including pancreatic, breast, brain, thyroid, prostate, and skin. [20][21][22][23][24][25][26][27][28][29][30][31][32] Disruption of the CXCL12/CXCR4 axis promotes mobilization of hematopoietic stem and progenitor cells (HSPCs) from the BM to the blood, facilitating the process of cell collection for transplantation. 10,[33][34][35][36][37][38][39][40] Ding et al and Greenbaum et al have shown that cell type-specific deletion of CXCL12 in the BM results has selective effects on different types of HSPCs, suggesting that proximity to Cxcl12-expressing cells influences HSPC function.…”

Section: Introductionmentioning

confidence: 99%

Ubiquitous overexpression of CXCL12 confers radiation protection and enhances mobilization of hematopoietic stem and progenitor cells

et al. 2020

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C‐X‐C motif chemokine ligand 12 (CXCL12; aka SDF1α) is a major regulator of a number of cellular systems, including hematopoiesis, where it influences hematopoietic cell trafficking, proliferation, and survival during homeostasis and upon stress and disease. A variety of constitutive, temporal, ubiquitous, and cell‐specific loss‐of‐function models have documented the functional consequences on hematopoiesis upon deletion of Cxcl12. Here, in contrast to loss‐of‐function experiments, we implemented a gain‐of‐function approach by generating a doxycycline‐inducible transgenic mouse model that enables spatial and temporal overexpression of Cxcl12. We demonstrated that ubiquitous CXCL12 overexpression led to an increase in multipotent progenitors in the bone marrow and spleen. The CXCL12+ mice displayed reduced reconstitution potential as either donors or recipients in transplantation experiments. Additionally, we discovered that Cxcl12 overexpression improved hematopoietic stem and progenitor cell mobilization into the blood, and conferred radioprotection by promoting quiescence. Thus, this new CXCL12+ mouse model provided new insights into major facets of hematopoiesis and serves as a versatile resource for studying CXCL12 function in a variety of contexts.

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“…NF-κB activity is known to play an important role in the expression of CXCR4 in human breast cancer cells, and the NF-κB-binding site is known to be found in the proximal region of the CXCR4 promoter [23,31]. Therefore, we evaluated the possible downregulation of CXCR4 by MIN via suppression of NF-κB.…”

Section: Discussionmentioning

confidence: 99%

Minecoside Modulates Cell Invasion via Regulation of CXCR4 Expression in Breast and Colon Cancer Cells

2020

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Metastasis, which is closely linked to cancer-related deaths, is a highly complex process. It is an organ-specific process and involves interactions between the host and cancer cells. CXC chemokine receptor 4 is known to be expressed in various tumors and the binding with CXC ligand 12 induces signaling in cancer cell survival, migration, and proliferation. Particularly, the CXC chemokine receptor 4/CXC ligand 12 axis is known to promote the metastasis of breast cancer. Thus, agents that can downregulate CXC chemokine receptor 4 expression have potential against cancer metastasis. Minecoside is an active compound extracted from Veronica peregrina L. It is widely distributed in Korea and has been used as a traditional drug for the treatment of various chronic diseases. However, the anticancer and anti-inflammatory effects of minecoside have yet to be clarified. In this study, we found that minecoside downregulates constitutive CXC chemokine receptor 4 expression in MDA-MB-231 breast cancer cells. This downregulation also occurred at the transcriptional level. Minecoside-mediated suppression of CXC chemokine receptor 4 expression inhibited CXC ligand 12-induced invasion of breast and colorectal cancer cells. Overall, our results suggest that minecoside can be a novel anticancer agent that can inhibit cancer metastasis through inhibition of CXC chemokine receptor 4 expression.

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Mechanisms by which CXCR4/CXCL12 cause metastatic behavior in pancreatic cancer

Cited by 35 publications

References 30 publications

Single Cell Transcriptomics of Pancreatic Cancer Precursors Demonstrates Epithelial and Microenvironmental Heterogeneity as an Early Event in Neoplastic Progression

Single Cell Transcriptomics of Pancreatic Cancer Precursors Demonstrates Epithelial and Microenvironmental Heterogeneity as an Early Event in Neoplastic Progression

Ubiquitous overexpression of CXCL12 confers radiation protection and enhances mobilization of hematopoietic stem and progenitor cells

Minecoside Modulates Cell Invasion via Regulation of CXCR4 Expression in Breast and Colon Cancer Cells

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