Stromal cell derived factor-1 and CXCR4 expression in colorectal cancer promote liver metastasis

Amara, Sameh; Chaar, Ines; Khiari, M.; Ounissi, Donia; Weslati, Marwa; Hmida, Abdelmajid Ben; Bouraoui, Saâdia

doi:10.3233/cbm-150531

Cited by 39 publications

(32 citation statements)

References 30 publications

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“…In contrast to these results, it was observed that in breast cancer, the high expression of SDF-1 was associated with increased overall survival [37][38][39][40]. In the case of colorectal cancer, there is a high heterogeneity across existing studies [26][27][28][29].…”

Section: Discussionmentioning

confidence: 99%

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Prognostic significance of SDF-1 in colorectal cancer depends on CD8+ T-cell density

Lalos

Tülek

Tosti

et al. 2020

Preprint

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Background: Since colorectal cancer (CRC) remains one of the most common malignancies, a tremendous amount of studies keep taking place in this field. Over the past 25 years, a notable part of the scientific community has focused on the association between the immune system and colorectal cancer. A variety of studies have shown that high densities of infiltrating CD8+ T cells are associated with improved disease-free and overall survival in colorectal cancer (CRC). Stromal cell-derived factor-1 (SDF-1) is a protein that regulates leukocyte trafficking and is variably expressed in several healthy and malignant tissues. There is strong evidence that SDF-1 has a negative prognostic impact on colorectal cancer (CRC). However, based on a significant correlation of SDF-1 and CD8+ T cells in a previous study (r=0.53, p<0.0001), we hypothesized that the prognostic significance of SDF-1 in CRC could depend on the immune microenvironment. Therefore, we explored the combined prognostic significance of SDF-1 expression and CD8+ T cell density in a large CRC collective. Methods: We analyzed a tissue microarray (TMA) of 613 patient specimens of primary CRCs by immunohistochemistry (IHC) for the expression of SDF-1 by tumor cells and tumor-infiltrating immune cells (TICs) and CD8+ T-cells. Besides, we analyzed the expression of SDF-1 at the RNA level in The Cancer Genome Atlas cohort (TCGA). Results: We found that the the combined high expression of SDF-1 and CD8+ T-cell infiltration shows a favorable 5-year overall survival rate (66%; 95%CI=48–79%) compared to tumors showing a high expression of CD8+ T-cells only (55%; 95%CI=45–64%; p=0.0004). High expression of SDF-1 and CD8+ T-cells infiltration was significantly associated with a favorable prognosis also in a validation group (p=0.016). Univariate and multivariate Hazard Cox regression survival analysis considering the combination of both markers revealed that the combined high expression of SDF-1 and CD8+ T cells was an independent, favorable, prognostic marker for overall survival (HR=0.34, 95%CI=0.17–0.66; p=0.002 and HR=0.45, 95%CI=0.23–0.89; p=0.021, respectively). In a spearman’s correlation analysis from the TCGA cohort, SDF-1 also correlated significantly with CD8+ T cells (r=0.28). Conclusions: SDF-1 high /CD8 high density represents an independent, favorable, prognostic condition in CRC, most likely due to an effective antigen-specific immune response.

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Section: Discussionmentioning

confidence: 99%

“…In the study we conducted, we hypothesized that the prognostic significance of SDF-1 could depend on the immune microenvironment in CRC [26][27][28][29]. To explore this hypothesis, we comparatively investigated the prognostic role of SDF-1 in human CRC in the context of CD8 + T-cell density.…”

Section: Introductionmentioning

confidence: 99%

Prognostic significance of SDF-1 in colorectal cancer depends on CD8+ T-cell density

Lalos

Tülek

Tosti

et al. 2020

Preprint

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“…This axis plays an important role in inflammatory cell infiltration, migration and organ development (9). CXCR4 is expressed in many cancers, such as breast cancer, prostate cancer, pancreatic cancer, colon cancer, ovarian cancer, neuroblastoma and glioma (10,11). We detected the expressions of CXCR4 in 60 cases of NSCLC tissues by immunohistochemical assay.…”

Section: Discussionmentioning

confidence: 99%

Role of the stromal cell derived factor-1/CXC chemokine receptor 4 axis in the invasion and metastasis of lung cancer and mechanism

et al. 2017

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“…In CRC has been demonstrated that abnormal expression of Chemokine (C-X-C motif) receptor 4 (CXCR4) plays a crucial role in the invasion and liver metastasis 12 . CXCR4 belongs to G protein-coupled receptor superfamily, which selectively binds to stromal cell-derived factor 1 (SDF-1, also called CXCL12) to promote cancer metastasis 13 .…”

Section: Introductionmentioning

confidence: 99%

Nodal-Induced L1CAM/CXCR4 Subpopulation Sustains Tumor Growth and Metastasis in Colorectal Cancer Derived Organoids.

Cave

Momblona

Sevillano

et al. 2020

Preprint

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BackgroundColorectal cancer (CRC) is currently the third leading cause for cancer-related mortality. Cancer stem cells have been implicated in colorectal tumor growth, but their specific role in tumor biology, including metastasis, is still uncertain.MethodsIncreased expression of L1CAM, CXCR4 and NODAL was identified in tumor section of patients with CRC and in Patients-derived-organoids (PDOs). The expression of L1CAM, CXCR4 and NODAL was evaluated using quantitative real-time PCR, western blotting, immunofluorescence, immunohistochemistry and flow cytometry. The effects of the L1CAM, CXCR4 and NODAL on tumor growth, proliferation, migration, invasion, colony-formation ability, metastasis and chemoresistance were investigated both in vitro and in vivo.Results We found that human colorectal cancer tissue contains cancer stem cells defined by L1CAMhigh/CXCR4high expression that is activated by Nodal in hypoxic microenvironment. This L1CAMhigh/CXCR4high population is tumorigenic, highly resistant to standard chemotherapy, and determines the metastatic phenotype of the individual tumor. Depletion of the L1CAMhigh/CXCR4high population drastically reduces the tumorigenic potential and the metastatic phenotype of colorectal tumors.ConclusionIn conclusion, we demonstrated that a subpopulation of migrating L1CAMhigh/CXCR4high is essential for tumor progression. Together, these findings suggest that strategies aimed at modulating the Nodal signaling could have important clinical applications to inhibit colorectal cancer-derived metastasis.

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Stromal cell derived factor-1 and CXCR4 expression in colorectal cancer promote liver metastasis

Cited by 39 publications

References 30 publications

Prognostic significance of SDF-1 in colorectal cancer depends on CD8+ T-cell density

Prognostic significance of SDF-1 in colorectal cancer depends on CD8+ T-cell density

Role of the stromal cell derived factor-1/CXC chemokine receptor 4 axis in the invasion and metastasis of lung cancer and mechanism

Nodal-Induced L1CAM/CXCR4 Subpopulation Sustains Tumor Growth and Metastasis in Colorectal Cancer Derived Organoids.

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