Abstract
CD55 has been revealed to have an important role in tumor genesis, and presence of small populations of cells with strong CD55 expression would be sufficient to predict poor prognosis of several tumors. In our study we revealed that CD55 is a novel target of hypoxia-inducible factor HIF-2α in neuroblastoma (NB) cells. We show that HIF-2α expression is sufficient to sustain stem-like features of NB cells, whereas CD55 protein upon HIF-2α expression contributes to growth of colonies and to invasion of cells, but not to stemness features. Interestingly, in NB tissues, CD55 expression is limited to quite a small population of cells that are HIF-2α positive, and the gene expression of CD55 in the NB data set reveals that the presence of CD55high affects prognosis of NB patients. The functional characterization of CD55-positive populations within heterogeneous NB monoclonal cell lines shows that CD55 has pro-invading and anti-adhesive properties that might provide the basis for the ability of solid tumors to survive as microscopic residual disease. The easy accessibility to CD55 membrane antigen will offer the possibility of a novel antibody approach in the treatment of recurrent tumors and will provide a ready target for antibody-based visualization in NB diagnosis and prognosis.
Highlights
Neuroblastoma (NB) is a childhood tumor derived from precursor or immature cells of the ganglionic lineage of the sympathetic nervous system (SNS).[1]
In our study we revealed that CD55 is a novel target of hypoxia-inducible factors (HIFs)-2α in addition, in NB, HIF-1α protein staining is related to hypoxic areas, NB cells and that CD55 expression downstream of HIF-2α expression is necessary for tumor cell growth and invasion
CD55 might be regulated by HIF, as a HIF-functional binding site has been identified on the CD55 promoter.[20]
Summary
Neuroblastoma (NB) is a childhood tumor derived from precursor or immature cells of the ganglionic lineage of the sympathetic nervous system (SNS).[1] The clinical NB hallmark is the large heterogeneity, with the likelihood of tumor progression varying widely according to stage, age at diagnosis and anatomical site. Some NBs could undergo spontaneous regression that is partially regulated by developmentally programmed neuronal cell death and/or neuronal differentiation.[2]. The stage of disease as formulated in the International. Neuroblastoma Staging System is considered a marker of tumor burden and underlying tumor biology. Children 418 months with stage 4 (metastatic) disease are at high risk for death from refractory disease. Children with localized tumors (stage 1–2–3) are almost always cured with radiation or chemotherapy.[3]
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