Chemokines and Cancer Progression: A Qualitative Review on the Role of Stromal Cell-derived Factor 1-alpha and CXCR4 in Endometrial Cancer

Felix, Ashley S.; Edwards, Robert P.; Bowser, Robert; Linkov, Faina

doi:10.1007/s12307-010-0042-7

Cited by 6 publications

(9 citation statements)

References 22 publications

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“…CXCR4 is a chemokine receptor (C-X-C chemokine receptor type 4), and an increased expression of this receptor has been related to cancer progression 43 44 . Stromal cell-derived factor 1α (SDF-1α) is a natural CXCR4 ligand, and the stimulation of CXCR4 by treatment with SDF-1α induces CXCR4 endocytosis and actin polymerisation 45 46 , leading to macropinocytotic cellular uptake 47 .…”

Section: Resultsmentioning

confidence: 99%

Active macropinocytosis induction by stimulation of epidermal growth factor receptor and oncogenic Ras expression potentiates cellular uptake efficacy of exosomes

Nakase

Kobayashi

Takatani‐Nakase

et al. 2015

Sci Rep

222

227

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Exosomes are approximately 100-nm vesicles that consist of a lipid bilayer of cellular membranes secreted in large quantities from various types of normal and disease-related cells. Endocytosis has been reported as a major pathway for the cellular uptake of exosomes; however, the detailed mechanisms of their cellular uptake are still unknown. Here, we demonstrate the active induction of macropinocytosis (accompanied by actin reorganisation, ruffling of plasma membrane, and engulfment of large volumes of extracellular fluid) by stimulation of cancer-related receptors and show that the epidermal growth factor (EGF) receptor significantly enhances the cellular uptake of exosomes. We also demonstrate that oncogenic K-Ras-expressing MIA PaCa-2 cells exhibit intensive macropinocytosis that actively transports extracellular exosomes into the cells compared with wild-type K-Ras-expressing BxPC-3 cells. Furthermore, encapsulation of the ribosome-inactivating protein saporin with EGF in exosomes using our simple electroporation method produces superior cytotoxicity via the enhanced cellular uptake of exosomes. Our findings contribute to the biological, pharmaceutical, and medical research fields in terms of understanding the macropinocytosis-mediated cellular uptake of exosomes with applications for exosomal delivery systems.

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Section: Resultsmentioning

confidence: 99%

Active macropinocytosis induction by stimulation of epidermal growth factor receptor and oncogenic Ras expression potentiates cellular uptake efficacy of exosomes

Nakase

Kobayashi

Takatani‐Nakase

et al. 2015

Sci Rep

222

227

View full text Add to dashboard Cite

show abstract

“…Especially in breast cancer, microarray analysis identified CXCR4 as one of critical genes that was enriched in metastasis breast tumor cells, and overexpression of CXCR4 alone significantly increased the chance of metastasis in lung tissue and bone tissue shown in in vivo test and clinical study [reviewed in (Felix et al, 2010;Furusato et al, 2010;Wendel et al, 2012)]. T140, the peptidic CXCR4 antagonist, resulted in a statistically eloquent reduction in pulmonary metastasis of MDA-MB-231 in severe combined immunodeficiency (SCID) mice (Tamamura et al, 2003).…”

Section: Introductionmentioning

confidence: 99%

Silibinin, a novel chemokine receptor type 4 antagonist, inhibits chemokine ligand 12-induced migration in breast cancer cells

et al. 2014

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“…Abnormal expression of chemokines or their receptors is positively correlated with the development, progression and metastasis of tumor cells ( 3 , 4 ). CXC chemokine receptor-4 (CXCR4) is highly expressed on the surface of several different types of tumors ( 5 ). CXCL12 (CXC motif chemokine 12) [also known as stromal cell-derived factor (SDF-1)] has been identified as the specific ligand of CXCR4 and it is likely that the CXCR4/CXCL12 axis is involved in the development, progression and metastasis of tumors ( 6 , 7 ).…”

Section: Introductionmentioning

confidence: 99%

Expression of CXC chemokine receptor-4 and forkhead box 3 in neuroblastoma cells and response to chemotherapy

et al. 2014

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Current evidence indicates that the abnormal expression of chemokines or their receptors, such as CXC chemokine receptor-4 (CXCR4), is positively correlated with the development, progression and metastasis of tumor cells. However, the role of CXCR4 in neuroblastoma and its response to chemotherapy remain largely unclear. In addition, forkhead box 3 (Foxp3), a transcription factor associated with T cell tolerance, is expressed in tumor cells and plays a role in the immune evasion of cancers. The present study aimed to examine the expression of CXCR4 and Foxp3 in the LAN-5 and SK-N-SH neuroblastoma cell lines. The effects of chemotherapy drugs, cyclophosphamide (CTX) and pirarubicin (THP), on the expression of these two genes were also investigated. Our findings indicated that CXCR4 and Foxp3 were highly expressed in LAN-5 and SK-N-SH cells. Following treatment with CTX and THP, the protein expression of CXCR4 in LAN-5 and SK-N-SH cells was significantly decreased (P<0.05). The expression of Foxp3 in LAN-5 cells was also significantly downregulated by CTX and THP treatment (P<0.05). Therefore, the high expression of CXCR4 and Foxp3 in LAN-5 and SK-N-SH cells and their subsequent downregulation following administration of the chemotherapy agents suggests that the chemokine receptors, CXCR4 and Foxp3, may be involved in the metastasis and tumor evasion of neuroblastoma. Further studies should investigate the expression of CXCR4 and Foxp3 in patient samples.

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Chemokines and Cancer Progression: A Qualitative Review on the Role of Stromal Cell-derived Factor 1-alpha and CXCR4 in Endometrial Cancer

Cited by 6 publications

References 22 publications

Active macropinocytosis induction by stimulation of epidermal growth factor receptor and oncogenic Ras expression potentiates cellular uptake efficacy of exosomes

Active macropinocytosis induction by stimulation of epidermal growth factor receptor and oncogenic Ras expression potentiates cellular uptake efficacy of exosomes

Silibinin, a novel chemokine receptor type 4 antagonist, inhibits chemokine ligand 12-induced migration in breast cancer cells

Expression of CXC chemokine receptor-4 and forkhead box 3 in neuroblastoma cells and response to chemotherapy

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