The prognostic significance and impact of the CXCR4-CXCR7-CXCL12 axis in primary cutaneous melanoma

McConnell, Adams A.; Ellis, Robert; Pathy, B; Plummer, Ruth; Lovat, Penny E.; O'Boyle, Graeme

doi:10.1111/bjd.14720

Cited by 35 publications

(26 citation statements)

References 31 publications

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“…Consistent with our ndings, McConnell et al demonstrated that patients with AJCC stage II melanomas had 3-fold risk of disease reoccurrence in individuals with high total CXCR4 expression (>50%). Nevertheless, CXCL12 over-expression in the adjacent epidermis of all melanoma stages with tumour progression was associated with increased time to metastasis [35]. Due to the autocrine and paracrine CXCL12 secretion, the contradictory phenomenon remains to be further studied.…”

Section: Discussionmentioning

confidence: 98%

CXCR4-CXCL12 axis and distant metastatic outgrowth in head and neck malignancy

Bahadori

Fritsche

et al. 2020

Preprint

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Background: To analyze whether distant metastatic outgrowth in different head and neck malignancies (HNM) underlies the CXCR4-CXCL12 axis as overriding molecular mechanism. Methods: Clinic-pathological data of 1,250 HNM was included. HNM were collected due to different capability to exhibit distant metastasis comprising basal cell, squamous cell, and adenoid-cystic carcinoma as well as melanoma. MMP2/9, TIMP1/2, CXCR4, and CXCL12 immunohistochemistry was done in 190 randomly selected specimens.Results: Immunohistochemistry visualized a significant increase in MMP2/9, TIMP1/2, CXCR4, and CXCL12 protein expression following the clinical occurrence of distant metastasis. CXCR4, CXCL12, and TIMP2-expression significantly increases with number of affected organs by distant metastasis. Cox regression demonstrated CXCR4-overexpression and advanced T-status being independent risk factors of distant metastasis associated death.Conclusion: The CXCR4-CXCL12 axis is associated with the occurrence of distant metastases in different HNM. The increased risk of distant metastasis associated death was identified at primary tumour site and, therefore, potentially influences further treatment protocols.

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Section: Discussionmentioning

confidence: 98%

CXCR4-CXCL12 axis and distant metastatic outgrowth in head and neck malignancy

Bahadori

Fritsche

et al. 2020

Preprint

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“…Furthermore, different crosstalk between MAFs and melanoma cells are involved in metastasis of melanoma cells. For example, CXCR4 (CXC chemokine receptor-4) is expressed on the surface of melanoma cells, while its ligand CXCL12 is released by MAFs in the tumor microenvironment, promoting the migration and metastasis of melanoma cells to distal metastatic sites through interaction with CXCR4 expressed on tumor cells ( 277 – 279 ). Besides, HGF secreted by MAFs induce fibronectin expression and associated matrix assembly, which promotes melanoma cell metastasis ( 280 ).…”

Section: Melanomamentioning

confidence: 99%

A Complex and Evolutive Character: Two Face Aspects of ECM in Tumor Progression

2020

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Tumor microenvironment, including extracellular matrix (ECM) and stromal cells, is a key player during tumor development, from initiation, growth and progression to metastasis. During all of these steps, remodeling of matrix components occurs, changing its biochemical and physical properties. The global and basic cancer ECM model is that tumors are surrounded by activated stromal cells, that remodel physiological ECM to evolve into a stiffer and more crosslinked ECM than in normal conditions, thereby increasing invasive capacities of cancer cells. In this review, we show that this too simple model does not consider the complexity, specificity and heterogeneity of each organ and tumor. First, we describe the general ECM in context of cancer. Then, we go through five invasive and most frequent cancers from different origins (breast, liver, pancreas, colon, and skin), and show that each cancer has its own specific matrix, with different stromal cells, ECM components, biochemical properties and activated signaling pathways. Furthermore, in these five cancers, we describe the dual role of tumor ECM: as a protective barrier against tumor cell proliferation and invasion, and as a major player in tumor progression. Indeed, crosstalk between tumor and stromal cells induce changes in matrix organization by remodeling ECM through invadosome formation in order to degrade it, promoting tumor progression and cell invasion. To sum up, in this review, we highlight the specificities of matrix composition in five cancers and the necessity not to consider the ECM as one general and simple entity, but one complex, dynamic and specific entity for each cancer type and subtype.

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“…Potential intracellular biomarkers associated with melanoma transformation. in stage II melanoma (66). Another potential intracellular biomarker is cytotoxic T-lymphocyte associated protein 4 (CTLA4), which is upregulated during the transformation to melanoma, and in the list of the top 50 modulated genes (Fig.…”

Section: Differential Expression Levelsmentioning

confidence: 99%

A meta‑analysis of transcriptome datasets characterizes malignant transformation from melanocytes and nevi to melanoma

et al. 2018

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Melanoma represents one of the most aggressive malignancies and has a high tendency to metastasize. The present study aims to investigate the molecular mechanisms of two pathways to cancer transformation with the purpose of identifying potential biomarkers. Our approach is based on a meta-analysis of gene expression profiling contrasting two scenarios: A model that describes a transformation pathway from melanocyte to melanoma and a second model where transformation occurs through an intermediary nevus. Data consists of three independent, publicly available microarray datasets from the Gene Expression Omnibus (GEO) database comprising samples from melanocytes, nevi and melanoma. The present analysis identified 808 differentially expressed genes (528 upregulated and 360 downregulated) in melanoma compared with nevi, and 2,331 differentially expressed genes (946 upregulated and 1,385 downregulated) in melanoma compared with melanocytes. Further analysis narrowed down this list, since 682 differentially expressed genes were found in both models (417 upregulated and 265 downregulated). Enrichment analysis identified relevant dysregulated pathways. This article also presented a discussion on significant genes including ADAM like decysin 1, neudesin neurotrophic factor, , apolipoprotein L6, motif chemokine ligand ()8, basic, immunoglobulin-like variable motif containing and . These are of particular interest because they encode secreted proteins hence represent potential blood biomarkers for the early detection of malignant transformation in both scenarios. Cytotoxic T-lymphocyte associated protein 4, an important therapeutic target in melanoma treatment, was also upregulated in both comparisons indicating a potential involvement in immune tolerance, not only at advanced stages but also during the early transformation to melanoma. The results of the present study may provide a research direction for studying the mechanisms underlying the development of melanoma, depending on its origin.

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The prognostic significance and impact of the CXCR4-CXCR7-CXCL12 axis in primary cutaneous melanoma

Abstract: CXCR4 expression defines a potential prognostic biomarker for AJCC stage II melanoma. Moreover, targeting the CXCR4-CXCR7-CXCL12 axis may represent a novel therapeutic strategy to prevent early melanoma progression.

Cited by 35 publications

References 31 publications

CXCR4-CXCL12 axis and distant metastatic outgrowth in head and neck malignancy

CXCR4-CXCL12 axis and distant metastatic outgrowth in head and neck malignancy

A Complex and Evolutive Character: Two Face Aspects of ECM in Tumor Progression

A meta‑analysis of transcriptome datasets characterizes malignant transformation from melanocytes and nevi to melanoma

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