Protein expression of the chemokine receptor CXCR4 and its ligand CXCL12 in primary cutaneous melanoma—biomarkers of potential utility?

Mitchell, Brendon C.; Leone, Dominick; Feller, Kyle; Menon, Sandeep; Bondzie, Philip A.; Yang, Shi; Park, Hee-Young; Mahalingam, Meera

doi:10.1016/j.humpath.2014.06.018

Cited by 14 publications

(25 citation statements)

References 22 publications

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“…In contrast to previous studies, reporting an apparent correlation of CXCR4 expression with melanoma ulceration, increased thickness, metastasis and morbidity, Mitchell et al . suggested that CXCR4 expression correlates with better prognostic features, such as the absence of mitosis or ulceration, tumour regression and early AJCC stage disease . However, data from the current study clearly demonstrate that elevated CXCR4 expression in melanoma significantly correlates with a metastatic phenotype.…”

Section: Discussioncontrasting

confidence: 62%

“…The gain of CXCR4 expression by melanoma cells not only permits migration towards CXCL12 at common metastatic sites, but may also promote tumour cell survival and proliferation through paracrine/autocrine‐mediated activation of MAPK cell signalling, highlighting a potential role for CXCR4–CXCL12 signalling in melanomagenesis . Furthermore, elevated CXCR4 expression has been linked to melanoma ulceration and thickness and disease progression, although to date CXCR4 expression as a prognostic biomarker remains ambivalent . Similarly, the role of the CXCL12 chemokine ligand within primary cutaneous melanomas has largely been overlooked.…”

mentioning

confidence: 99%

“…Importantly, CXCL12 functions to shape the primary tumour infiltrate, promoting angiogenesis by recruiting potent proangiogenic plasmacytoid dendritic cells or creating an immunosuppressive tumour microenvironment through recruitment of CD4 + T regulatory cells . However the effect of CXCL12 within the local microenvironment of primary cutaneous melanoma remains unexplored, with only one study reporting an apparent correlation between the absence of tumoral expression and poor prognosis …”

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confidence: 99%

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

et al. 2016

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Section: Discussioncontrasting

confidence: 62%

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confidence: 99%

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confidence: 99%

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

et al. 2016

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“…107 Cutaneous malignancies in which CXCR4 is thought to play a functional role include but are not limited to cSCC, dermatofibrosarcoma, merkel cell carcinoma, and melanoma. [108][109][110][111] Of these, the prognostic implications of CXCR4 are best understood in melanoma, where its expression was first observed in primary melanomas and pulmonary metastasis in mouse models by Murakami et al in 2002. 112 Since then, multiple studies have found CXCR4 expression to be associated with ulceration, tumor thickness, lymph node metastasis, and increasing mortality, suggesting that CXCR4 expression may serve as a prognosticator of poor outcome.…”

Section: Other Potential Players: a Role For Ncam And Cxcr4?mentioning

confidence: 99%

“…[113][114][115] In contrast, other studies, including our own, have failed to find associations between CXCR4 expression and poor outcomes or negative histopathologic prognosticators. 111,116,117 Thus the status of CXCR4 as a prognostic indicator remains equivocal.…”

Section: Other Potential Players: a Role For Ncam And Cxcr4?mentioning

confidence: 99%

Desmoplastic Melanoma, Neurotropism, and Neurotrophin Receptors—What We Know and What We Do Not

Frydenlund

Mahalingam²

2015

Advances in Anatomic Pathology

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Desmoplastic melanoma (DM) is a relatively rare cytomorphologic variant of melanoma with a marked propensity for perineural invasion (PNI). Historically, DMs that display PNI have been grouped under the umbrella term of neurotropic melanoma (NM). However, definitions for NM and desmoplastic NM are not consistent in the literature, presenting a barrier to a comprehensive understanding of these lesions. In this review, we parse the literature on DM, NM, and desmoplastic NM, to clarify definitions and ascertain the incidence of PNI, with a view toward understanding its prognostic relevance. Neurotrophins, which represent a family of signaling peptides important to the development and maintenance of the peripheral nervous system, have been implicated in the pathogenesis of PNI in select lineage-unrelated malignancies. Given this, we also detail evidence linking neurotrophins and their receptors (TrkA, RET, p75NGFR, and NCAM) to the pathogenesis of PNI in melanoma.

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Chemokines as possible therapeutic targets in metastatic melanoma

et al. 2023

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Background Cutaneous melanoma is a relentless form of cancer which continues to rise in incidence. Currently, cutaneous melanoma is the leading cause of skin cancer‐related mortality, which can mainly be attributed to its metastatic potential. The activation of chemokine axes is a major contributor to melanoma metastasis through its involvement in promoting tumour cell migration, proliferation, survival, and adhesion. This review will focus on the role of chemokines in melanoma and possible therapeutic strategies to alter chemokine activation and subsequently inhibit the activation of signalling cascades that may promote metastasis. Methods A literature review was conducted to evaluate chemokines as possible therapeutic targets in metastatic melanoma. Results The crosstalk between signalling pathways and immune responses in the melanoma microenvironment resembles a complex and dynamic system. Therefore, the involvement of governing chemokine axes in the promotion of cutaneous and metastatic melanoma demands a proper understanding of the tumour microenvironment in order to identify possible targets and develop appropriate treatments against melanoma. Conclusion Even though chemokine axes are regarded as promising therapeutic targets, it has become increasingly evident that chemokines can play a critical role in both tumour inhibition and promotion. The inhibition of chemokine axes to inhibit signalling cascades in target cells that regulate metastasis should, therefore, be carefully approached.

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Protein expression of the chemokine receptor CXCR4 and its ligand CXCL12 in primary cutaneous melanoma—biomarkers of potential utility?

Cited by 14 publications

References 22 publications

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

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

Desmoplastic Melanoma, Neurotropism, and Neurotrophin Receptors—What We Know and What We Do Not

Chemokines as possible therapeutic targets in metastatic melanoma

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