Abstract
Melanoma cell expression of the nerve growth factor receptor CD271 is associated with stem-like properties. However, the contributing role of the receptor in melanoma cell migration is elusive. Here, we explored extracranial (skin, soft tissue, lymph node and liver, n = 13) and matched brain metastases (BM, n = 12) and observed a heterogeneous distribution of phenotypically distinct subsets of CD271+ cells. In addition, we observed that CD271 expression gradually rises along with melanoma progression and metastasis by exploration of publicly available expression data of nevi, primary melanoma (n = 31) and melanoma metastases (n = 54). Furthermore, we observed highest levels of CD271 in BM. Sub-clustering identified 99 genes differentially expressed among CD271high and CD271low (p < 0.05) BM-subgroups. Comparative analysis of subsets revealed increased ( ≥ 1.5fold, log2) expression of migration-associated genes and enrichment of CD271-responsible genes involved in DNA-repair and stemness. Live cell-imaging based scratch-wound assays of melanoma cells with stable knock-down of CD271 revealed a significantly reduced cell migration (3.9fold, p = 1.2E-04) and a reduced expression of FGF13, CSPG4, HMGA2 and AKT3 major candidate regulatory genes of melanoma cell migration. In summary, we provide new insights in melanoma cell migration and suggest that CD271 serves as a candidate regulator, sufficient to determine cellular properties of melanoma brain metastatic cells.
Highlights
Melanoma cell expression of the nerve growth factor receptor CD271 is associated with stem-like properties
To explore whether CD271+ melanoma cells are prone to metastasize to the brain, we analyzed matched pairs of primary tumors (n = 2), extracranial (n = 13) and brain metastasis (n = 12) as well as unmatched brain (n = 7) and extracranial (n = 1) metastases of melanoma for expression of CD271, irrespective of the BRAF mutation status and therapeutic interventions (Supplementary information, SI; Table S1)
Metastasis to the brain is frequently observed in melanoma patients and most likely presents a homing process of melanoma cells governed by specific cytokines or growth factors supplied by the brain tissue[45]
Summary
Melanoma cell expression of the nerve growth factor receptor CD271 is associated with stem-like properties. Melanoma cells feature a high migratory phenotype[3] facilitating the colonization of distant organs e.g. lung, liver, heart, peritoneum, small intestine, spleen and brain[4]. Despite this broad spectrum of possibly involved organs, brain metastases are very common, observed in 20–40% of melanoma patients. The expression of nerve growth factor receptor CD271 was associated with increased incidence of melanoma brain metastases[9] as well as metastases in lung, liver and kidney[10]. CD271+ cells represent a cellular sub-set highly capable of migrating and infiltrating the brain parenchyma[17] It remains elusive whether CD271+ cells present a cell subpopulation prone to metastasize to the brain. We explored the presence and distribution of CD271 expressing cells in primary melanoma as well as in extracranial, solitary and multiple brain metastases and elucidated the potential role of CD271 in melanoma brain tropism
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
