Emerging roles of the CXCL12/CXCR4 axis in pancreatic cancer progression and therapy

Neilsen, Beth K.; Li, Jing; Steele, Maria M.; Singh, Rakesh K.; Hollingsworth, Michael A.; Oupický, David

doi:10.1016/j.pharmthera.2017.05.012

Cited by 143 publications

(102 citation statements)

References 222 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 No reuse allowed without permission.(which was not peer-reviewed) is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity.The copyright holder for this preprint .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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“…It has also been reported that interactions between CXCR4 and SDF-1 lead to activation of G protein-mediated signaling pathways and downregulation of RAS and PI3 kinase to affect cell motility (21,22). Furthermore, CXCR4/SDF-1 complexes have been shown to activate protein kinase B, mitogen-activated protein kinases, and nuclear factor kappa B in combination with phosphatidylinositol 3-kinases or Src family kinases and other downstream signaling proteins to promote the expression of heparanase and metalloproteinase-9 and degradation of extracellular matrix (23). As a result, tumor cells can gain access to adjacent tissues as part of tumor invasion and metastasis processes (23).…”

Section: Discussionmentioning

confidence: 99%

“…Furthermore, CXCR4/SDF-1 complexes have been shown to activate protein kinase B, mitogen-activated protein kinases, and nuclear factor kappa B in combination with phosphatidylinositol 3-kinases or Src family kinases and other downstream signaling proteins to promote the expression of heparanase and metalloproteinase-9 and degradation of extracellular matrix (23). As a result, tumor cells can gain access to adjacent tissues as part of tumor invasion and metastasis processes (23). In the present study, our data showed that CXCR4 silencing regulates the hallmarks of the metastasis process by inhibiting colony formation, cell proliferation, migration and invasive in PC9 and PC14 cell lines.…”

Section: Discussionmentioning

confidence: 99%

Plasma exo-hsa_circRNA_0056616: A potential biomarker for lymph node metastasis in lung adenocarcinoma

He¹,

Zhong²,

Zheng³

et al. 2020

J. Cancer

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Background: To investigate the relationship between CXCR4-related circular RNAs (circRNAs) in exosomes and lymph node metastasis of lung adenocarcinoma. Methods: Totally 41 lung adenocarcinoma tissues (21 with lymph node metastasis and 20 without) were collected. Expression of CXCR4 protein was detected by western blotting analysis. A stable PC9/CXCR4-shRNA and PC14/CXCR4-shRNA knockdown lung adenocarcinoma cell lines were established and subjected to functional assays (cell proliferation, colony formation, migration and invasion) for phenotype changes. Exo-hsa-circRNAs (has-circRNAs in exosomes) were detected in vivo and in vitro. The diagnostic value of differentially expressed exo-has-circRNAs was evaluated. Results: Expression levels of CXCR4 were higher in patients with lymph node metastasis than in those without (P = 0.001). Silencing CXCR4 expression in PC9 and PC14 cell lines with short hairpin RNA could effectively abolish colony formation frequency, proliferation rate, migration rate, and the number of invasive cells (all P < 0.001). Exo_circRNA_0056616 was detected in both PC-9/CXCR4-shRNA cells and lung adenocarcinoma plasma at significantly higher levels than in the corresponding control (P < 0.001). When a receiver operating characteristic (ROC) curve for plasma exo-hsa_circRNA_0056616 levels and diagnosis of lymph node metastasis of lung adenocarcinoma was generated, a cutoff value of 0.394 was identified with an area under the curve of 0.812 (95% confidence interval 0.720-0.903), a sensitivity of 0.792, and specificity of 0.810. Conclusions: Taken together, our findings suggested that CXCR4 was higher in the lung adenocarcinoma tissues with lymph node metastasis. Higher plasma levels of exo-hsa_circRNA_0056616 in these patients also suggest that this circRNA represents a potential biomarker for lymph node metastasis predictor in lung adenocarcinoma.

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“…Treatment with F-PCX@PFC/siSTAT3 displayed the least Ki67 staining among all the treatments, confirming the results from Figure 5. [20] CXCR4 effect on the expression of MMPs may further promote angiogenesis. Tumors secrete VEGF to promote local angiogenesis required for continued growth.…”

Section: Anti-angiogenic and Anti-proliferation Effect Of The Treatmementioning

confidence: 99%

Perfluorocarbon Nanoemulsions for Combined Pulmonary siRNA Treatment of Lung Metastatic Osteosarcoma

Shen

Wang

et al. 2019

Advanced Therapeutics

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Lung metastatic osteosarcoma is a lethal disease afflicting children and adolescents, with a 5-year survival rate of less than 20%. The development of perfluorocarbon (PFC) nanoemulsions as systems for direct pulmonary delivery of combination drug/siRNA therapy is reported. Fluorinated polycation (F-PCX) with an inherent ability to inhibit C-X-C receptor type 4 (CXCR4) is synthesized and used as a surfactant in the preparation of F-PCX@PFC nanoemulsions. The nanoemulsions are loaded with siRNA against signal transducer and activator of transcription 3 (STAT3) for combined treatment of lung metastasis in osteosarcoma. Intratracheal instillation of the treatments significantly prolonged the survival of animals with established lung metastases. The treatment with F-PCX@PFC/siSTAT3 emulsion polyplexes decreased the number of myeloid-derived suppressor cells (MDSCs) and regulatory T cells (Tregs) in the tumors, while increasing CD8 + T cells infiltration andIFNγ secretion to overcome the immunosuppressive tumor microenvironment. The reported nanoemulsions represent a promising pulmonary treatment of lung metastatic osteosarcoma.

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Emerging roles of the CXCL12/CXCR4 axis in pancreatic cancer progression and therapy

Cited by 143 publications

References 222 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

Plasma exo-hsa_circRNA_0056616: A potential biomarker for lymph node metastasis in lung adenocarcinoma

Perfluorocarbon Nanoemulsions for Combined Pulmonary siRNA Treatment of Lung Metastatic Osteosarcoma

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