2017
DOI: 10.1016/j.pharmthera.2017.05.012
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Emerging roles of the CXCL12/CXCR4 axis in pancreatic cancer progression and therapy

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Cited by 148 publications
(102 citation statements)
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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%
“…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%
“…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%
“…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%