CXCL13-CXCR5 axis promotes the growth and invasion of colon cancer cells via PI3K/AKT pathway

Zhu, Zhenyu; Zhang, Xukui; Guo, Hongbo; Fu, Ling; Pan, Ganlin; Sun, Yanyan

doi:10.1007/s11010-014-2285-y

Cited by 83 publications

(58 citation statements)

References 26 publications

(28 reference statements)

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“…Among various chemokines, C-X-C motif ligand 13 (CXCL13, also named as B-cell attracting chemokine 1 (BCA-1)) is thought to play an important pro-tumor role in colon, prostate, and breast cancers through the interaction with its receptor, the C-X-C chemokine receptor 5 (CXCR5) [ 12 - 14 ]. In particular, a recent in vitro study with colorectal cancer cell lines reported the interaction of CXCL13 with CXCR5 activated the phosphatidylinositol-3 kinase (PI3K)/AKT pathway leading to migration and invasion of cancer cells [ 15 ]. In NHL, a recent prospective study of inflammatory markers demonstrated a significant association of serum CXCL13 with the risk of lymphoma supporting its role in the lymphoma development [ 16 ].…”

Section: Introductionmentioning

confidence: 99%

The serum CXCL13 level is associated with the Glasgow Prognostic Score in extranodal NK/T-cell lymphoma patients

et al. 2015

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BackgroundThe Glasgow Prognostic Score (GPS) measures inflammation and proves its prognostic value in patients with extranodal natural killer (NK)/T-cell lymphoma (ENKTL) which is commonly combined with inflammatory lesion. Given inflammatory chemokines play an important role in tumor progression, we hypothesized that chemokines might influence ENKTL aggressiveness through interaction with their receptors in the tumor tissue.MethodsWe measured the serum levels of C-X-C motif ligand 13 (CXCL13) in 69 patients with ENKTL who received non-anthracycline-based chemotherapy and/or concurrent chemoradiotherapy because CXCL13 is thought to have a pro-tumor effect through interaction with its receptor, the C-X-C chemokine receptor 5 (CXCR5). We analyzed the association of serum CXCL13 with the GPS, and their prognostic relevance. The levels of CXCL13 were measured using a multiplex chemokine assay on archived frozen serum samples.ResultsPatients were categorized into high and low CXCL13 groups if they had CXCL13 levels above or below the median value of 29.1 pg/mL, respectively. The high CXCL13 group and grouping by the GPS showed a significant association with poor progression-free survival. The elevated serum levels of CXCL13 were also significantly associated with a high score of the GPS. High CXCL13 levels and GPS were significantly associated with high tumor burden predicting poor prognosis including stages III/IV, extranasal presentation, bone marrow invasion, and presence of Epstein-Barr virus (EBV) DNA in blood. Furthermore, serum CXCL13 and GPS discriminated patients at risk of treatment failure among patients with low tumor burden (stage I/II) and non-detectable EBV DNA.ConclusionsSerum levels of CXCL13 were associated with the prognostic value of GPS. Grouping by the serum CXCL13 might predict survival outcomes in patients with ENKTL, suggesting that it is a potential therapeutic target.

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Section: Introductionmentioning

confidence: 99%

The serum CXCL13 level is associated with the Glasgow Prognostic Score in extranodal NK/T-cell lymphoma patients

et al. 2015

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“…CXCL-13, which expressed in lymphoid organs and some tumor tissues, has attracted a lot of attention for its important role in attracting tumor cells spreading to these sites and promoting bad clinical outcomes [17,27,28]. Zhu et al [29] study showed CXCL-13 promoted colon cancer cells growth and migration via activating the PI3K/AKT pathway. Furthermore, CXCL-13 promoted matrix metalloproteinase 13 expression and secretion.…”

Section: Discussionmentioning

confidence: 99%

CXCL-13 Regulates Resistance to 5-Fluorouracil in Colorectal Cancer

et al. 2020

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Purpose5-Fluorouracil (5-Fu) is used as a conventional chemotherapy drug in chemotherapy for patients with advanced colorectal cancer, but many patients still suffer from treatment failure due to 5-Fu resistance. Emerging observations revealed the important role of chemokine (C-X-C motif) ligand 13 (CXCL-13) in tumor microenvironment and its relationship with prognosis in patients with colorectal cancer. This study is designed to reveal the important role of CXCL-13 in causing colorectal cancer resistance to 5-Fu.Materials and MethodsCXCL-13 levels of patient's serum or cell culture supernatants were measured separately by enzyme-linked immunosorbent assay. In cell assays, cell viability is detected by Cell Counting Kit-8. Therefore, the recombinant human CXCL-13 was used to simulate its high expression in cells while its antibody and siRNA were used to reduce CXCL-13 expression in cells.ResultsIn this study, we demonstrated that CXCL-13 is associated with 5-Fu resistance by culture medium exchange experiments and cytokine arrays of colorectal cancer resistant and nonresistant cells. Clinical studies showed that CXCL-13 is highly expressed in the serum of 5-Fu–resistant patients. High levels of serum CXCL-13 also predict a worse clinical outcome. The addition of recombinant CXCL-13 cytokine resulted in 5-Fu resistance, while its antibody overcame 5-Fu resistance, and knockdown of CXCL-13 expression by siRNA also reduced 5-Fu resistance, which can be saved by added recombination CXCL-13.ConclusionThese results not only identify a CXCL-13 mediated 5-Fu resistance mechanism but also provide a novel target for 5-Fu–resistant colorectal cancer in prevention and treatment strategies.

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“…The role of B-cells, and its supporting cell types in immunosurveillance is complex and dichotomous. On one hand, animal models studies suggest participation in proliferation and metastasis by promoting chronic inflammation, and suppressing antitumor responses [38], while on the other hand, promote long term survival leading to increased intratumor densities of tumor infiltrating immune cells suppressing tumorigenesis [39]. MS4A1 (CD20, tumor infiltrating B-cell marker), and BACH2 (a well-known transcriptional regulator of B and TFH cells), two genes previously implicated in contributing to immune landscape differences between RSCC and LSCC [39], are more predominantly suppressed within distal tumors.…”

Section: Suppressed Immune Signaling Predominates Left-sided Colon Tumentioning

confidence: 99%

Right and left-sided colon cancers - specificity of molecular mechanisms in tumorigenesis and progression

et al. 2020

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Background: Given the differences in embryonic origin, vascular and nervous supplies, microbiotic burden, and main physiological functions of left and right colons, tumor location is increasingly suggested to dictate tumor behavior affecting pathology, progression and prognosis. Right-sided colon cancers arise in the cecum, ascending colon, hepatic flexure and/or transverse colon, while left-sided colon cancers arise in the splenic flexure, descending, and/or sigmoid colon. In contrast to prior reports, we attempt to delineate programs of tumorigenesis independently for each side. Methods: Four hundred and eleven samples were extracted from The Cancer Genome Atlas-COAD cohort, based on a conservative sample inclusion criterion. Each side was independently analyzed with respect to their respective normal tissue, at the level of transcription, post-transcription, miRNA control and methylation in both a stage specific and stage-agnostic manner. Results: Our results indicate a suppression of enzymes involved in various stages of carcinogen breakdown including CYP2C8, CYP4F12, GSTA1, and UGT1A within right colon tumors. This implies its reduced capacity to detoxify carcinogens, contributing to a genotoxic tumor environment, and subsequently a more aggressive phenotype. Additionally, we highlight a crucial nexus between calcium homeostasis (sensing, mobilization and absorption) and immune/GPCR signaling within left-sided tumors, possibly contributing to its reduced proliferative and metastatic potential. Interestingly, two genes SLC6A4 and HOXB13 show opposing regulatory trends within right and left tumors. Post-transcriptional regulation mediated by both RNA-binding proteins (e.g. NKRF (in left) and MSI2 (in right)) and miRNAs (e.g. miR-29a (in left); miR-155, miR181-d, miR-576 and miR23a (in right)) appear to exhibit side-specificity in control of their target transcripts and is pronounced in right colon tumors. Additionally, methylation results depict location-specific differences, with increased hypomethylation in open seas within left tumors, and increased hypermethylation of CpG islands within right tumors. Conclusions: Differences in molecular mechanisms captured here highlight distinctions in tumorigenesis and progression between left and right colon tumors, which will serve as the basis for future studies, influencing the efficacies of existing and future diagnostic, prognostic and therapeutic interventions.

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CXCL13-CXCR5 axis promotes the growth and invasion of colon cancer cells via PI3K/AKT pathway

Cited by 83 publications

References 26 publications

The serum CXCL13 level is associated with the Glasgow Prognostic Score in extranodal NK/T-cell lymphoma patients

The serum CXCL13 level is associated with the Glasgow Prognostic Score in extranodal NK/T-cell lymphoma patients

CXCL-13 Regulates Resistance to 5-Fluorouracil in Colorectal Cancer

Right and left-sided colon cancers - specificity of molecular mechanisms in tumorigenesis and progression

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