CD271 determines migratory properties of melanoma cells

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.

CD271+ Cells Are Diagnostic and Prognostic and Exhibit Elevated MAPK Activity in SHH Medulloblastoma

“…This is an interesting finding and is supported by both the RNA sequencing data as well as the decrease in UI226 cell migration following selumetinib treatment in our 3D collagen assays. CD271 is associated with increased cell migration, invasion, and/or metastasis in several cancers (21,22,50,51). Recent studies have even shown that CD271 regulates "phenotypic switching" in melanoma by decreasing proliferation while simultaneously increasing invasion through two completely independent mechanisms (52).…”

Melanoma types by in vivo reflectance confocal microscopy correlated with protein and molecular genetic alterations: A pilot study

“…[4,5] For example, CM cell expression of the nerve growth factor receptor CD271 is associated with stem-like properties involving the epithelialmesenchymal transition, leading to dissemination and invasion of tumor cells. [6,7] It is also well known that tumor cells express antigens that can be recognized by the immune system, inducing an antitumor response that may affect microenvironment. Among different types of immune cells with specific prognostic significance, including T cells, B cells, NK cells and macrophages, the CD20+ B cells have been proven to play an important part in tumor progression, modulating normal cells in favour of tumor cell survival.…”

Cancer stem cells, stemness markers and selected drug targeting: metastatic colorectal cancer and cyclooxygenase-2/prostaglandin E2 connection to WNT as a model system

“…Moreover, the expression levels of PD-L1 and CD271 on the melanoma cells were both increased by IFN γ such that PD-L1 levels were related to those of CD271, and together with PD-L1 strongly and additively suppressed melanoma specific CTL activation [131] . CD271 expression on melanoma cells has also been linked to p53 activity, the DNA damage response and chemotherapeutic drug resistance as well as migratory properties to form metastases [132][133][134] . The higher expression levels of CD271 may determine specific properties of brain trophic metastatic melanoma cells [135,136] .…”