Nuclear Pattern of CXCR4 Expression Is Associated with a Better Overall Survival in Patients with Gastric Cancer

Nikkhoo, Bahram; Jalili, Ali; Fakhari, Shohreh; Sheikhesmaili, Farshad; Fathi, Fardin; Rooshani, Daem; Feizi, Mohammad Ali Hoseinpour; Nikzaban, Mehrnoush

doi:10.1155/2014/808012

Cited by 17 publications

(13 citation statements)

References 24 publications

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“…CXCL12 and CXCR4 are usually predominantly expressed on cell membrane or in the cytoplasm, although CXCL12 can also be secreted as a soluble form and CXCR4 sometimes still appears in the nucleus of GC cells . In AGS cells, CXCR4 has been identified at high levels in both cytoplasm and nucleus, but low on cell membrane . KATO III cell line similarly expresses low level of membrane CXCR4, which shows specific migratory but no proliferative or anti‐apoptotic activities in response to CXCL12 .…”

Section: Expression Of Cxcl12/cxcr4 Axis In Gcmentioning

confidence: 99%

“…As for MKN‐28, MKN‐45, MKN‐74, and SNU‐16 cells, CXCR4 is abundant in the cytoplasm but absent on cell membrane, which results in neither migratory, nor proliferative and survival responses to CXCL12 . In primary GC tissues, CXCR4 is generally strongly expressed in both the cytoplasm and the nucleus . But in diffuse‐type GC, including signet‐ring cell carcinoma, CXCR4 staining is usually seen in the nucleus and scant in the cytoplasm .…”

Section: Expression Of Cxcl12/cxcr4 Axis In Gcmentioning

confidence: 99%

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Inhibition of CXCL12/CXCR4 axis as a potential targeted therapy of advanced gastric carcinoma

et al. 2017

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The whole outcome for patients with gastric carcinoma (GC) is very poor because most of them remain metastatic disease during survival even at diagnosis or after surgery. Despite many improvements in multiple strategies of chemotherapy, immunotherapy, and targeted therapy, exploration of novel alternative therapeutic targets is still warranted. Chemokine receptor 4 (CXCR4) and its chemokine ligand 12 (CXCL12) have been identified with significantly elevated levels in various malignancies including GC, which correlates with the survival, proliferation, angiogenesis, and metastasis of tumor cells. Increasing experimental evidence suggests an implication of inhibition of CXCL12/CXCR4 axis as a promising targeted therapy, although there are rare trials focused on the therapeutic efficacy of CXCR4 inhibitors in GC until recently. Therefore, it is reasonable to infer that specific antagonists or antibodies targeting CXCL12/CXCR4 axis alone or combined with chemotherapy will be effective and worthy of further translational studies as a potential treatment strategy in advanced GC.

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Section: Expression Of Cxcl12/cxcr4 Axis In Gcmentioning

confidence: 99%

Section: Expression Of Cxcl12/cxcr4 Axis In Gcmentioning

confidence: 99%

Inhibition of CXCL12/CXCR4 axis as a potential targeted therapy of advanced gastric carcinoma

et al. 2017

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“…Downregulation of SDF-1 α also has been reported in colonic carcinoma [21] and human astrocytoma [22]. In continuation with these reports, Nikkhoo et al [23] have demonstrated recently that nuclear expression CXCR4 is associated with a better overall survival of patients with gastric cancer. These literatures regarding CXCR4 indicate that CXCR4 signaling is not limited to promote tumor progression only; it is also involved in maintaining normal homeostasis of cells/tissue.…”

Section: Introductionmentioning

confidence: 75%

Epigenetic Silencing of CXCR4 Promotes Loss of Cell Adhesion in Cervical Cancer

Yadav

Prasad

Das

et al. 2014

BioMed Research International

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In the network of chemokine signaling pathways, recent reports have described the SDF-1α/CXCR4 axis and its role in cancer progression and metastasis. Interestingly, we found downregulation of CXCR4 at both transcript and protein level in cervical cancer cell lines and primary tumors. We also found CXCR4 promoter hypermethylation in cervical cancer cell lines and primary biopsy samples. DNA hypomethylating drug 5-AZA-2′-deoxycytidine and histone deacetylase inhibitor Trichostatin A treatments in cell lines reactivate both CXCR4 transcription and protein expression. Cell adhesion assay demonstrated that autocrine SDF-1α promotes the loss of cell adhesion while paracrine SDF-1α predominantly protects the normal cervical cells from loss of cell adhesion. Cervical cancer cell line C-33A having increased expression of CXCR4 after TSA treatment showed increased cell adhesion by paracrine source of SDF-1α in comparison to untreated C-33A. These findings demonstrate the first evidence that epigenetic silencing of CXCR4 makes the cells inefficient to respond to the paracrine source of SDF-1α leading to loss of cell adhesion, one of the key events in metastases and progression of the disease. Our results provide novel insight of SDF-1α/CXCR4 signaling in tumor microenvironment which may be promising to further delineate molecular mechanism of cervical carcinogenesis.

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“…Discrepancies between chemokine expression by immunohistochemical evaluation and mRNA level have been reported. 18,31 Last, and most important, increased chemokine receptor expression in the primary tumor may be sufficient for homing to the metastatic site with no need for further upregulation upon arrival.…”

Section: Discussionmentioning

confidence: 99%

Chemokine Receptor Expression Pattern Correlates to Progression of Conjunctival Melanocytic Lesions

Ipenburg

Waard

Naus

et al. 2019

Invest. Ophthalmol. Vis. Sci.

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Citation: van Ipenburg JA, de Waard NE, Naus NC, Jager MJ, Paridaens D, Verdijk RM. Chemokine receptor expression pattern correlates to progression of conjunctival melanocytic lesions. Invest Ophthalmol Vis Sci. 2019;60:2950-2957. https://doi.org/ 10.1167 PURPOSE. Chemokines play a role in the progression and metastatic spread of both cutaneous and uveal melanomas. The aim of this study was to examine the prognostic value of expression of chemokine receptors CCR7, CXCR4, and CCR10 in conjunctival melanocytic lesions. METHODS.In total, 44 conjunctival nevi, 21 cases of primary acquired melanosis (PAM) with atypia and 35 conjunctival melanomas, were included. After immunohistochemical staining for CCR7, CXCR4, and CCR10 the immunoreactive score (IRS) was determined. The findings were correlated for association with melanoma and development of metastasis. For mechanistic evaluation, we used a mouse melanoma metastasis model using two human conjunctival melanoma cell lines, CM2005.1 and CRMM1.RESULTS. All tested chemokines showed a significantly higher expression in conjunctival melanoma than conjunctival nevi. There was a statistically significant difference between the IRS in nevi and PAM with atypia for nuclear IRS in CCR10 (P ¼ 0.03) and both nuclear and cytoplasmic IRS in CXCR4 (P < 0.01 and P ¼ 0.03, respectively); this was also true evaluating the groups PAM with atypia and melanoma all together (P < 0.01). Furthermore, a trend for lower IRS was seen in cases of melanoma without metastasis, with a suggestive pattern of a higher IRS in cases that did develop metastases, supported for CXCR4 using the mouse melanoma metastasis model. CONCLUSIONS.Expression of specific chemokines changes during the progression and metastatic spread of conjunctival melanocytic lesions. Differential chemokine profiles may hold prognostic value for patients with conjunctival melanomas and might be considered as a therapeutic target.

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Nuclear Pattern of CXCR4 Expression Is Associated with a Better Overall Survival in Patients with Gastric Cancer

Cited by 17 publications

References 24 publications

Inhibition of CXCL12/CXCR4 axis as a potential targeted therapy of advanced gastric carcinoma

Inhibition of CXCL12/CXCR4 axis as a potential targeted therapy of advanced gastric carcinoma

Epigenetic Silencing of CXCR4 Promotes Loss of Cell Adhesion in Cervical Cancer

Chemokine Receptor Expression Pattern Correlates to Progression of Conjunctival Melanocytic Lesions

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