Abstract：
:Neuronal pentraxins (NPTX) and their corresponding receptors (NPTXR) have been studied as synapse-associated proteins in the nervous system, but their role in cancer is largely unknown. By applying a multidisciplinary, high-throughput proteomic approach, we have recently identified a peptide ligand motif for targeted drug delivery to neuroblastoma. Here, we report the sequence similarity between this peptide and a conserved portion of the pentraxin domain that is involved in the homo- and hetero-oligomerization of NPTX2 and NPTXR. We show that, in comparison with normal tissues, NPTX2 and NPTXR are overexpressed in vivo in mouse models, as well as in human Schwannian stroma-poor, stage IV neuroblastoma. Both proteins are concentrated in the vicinity of tumor blood vessels, with NPTXR also present on neuroblastic tumor cells. In vivo targeting of NPTX2 and NPTXR with the selected peptide or with specific antibodies reduces tumor burden in orthotopic mouse models of human neuroblastoma. In vitro interference with this ligand/receptor system inhibits the organization of neuroblastoma cells in tumor-like masses in close contact with vascular cells, as well as their adhesion to normal microenvironment-derived cells, suggesting a role in the cross-talk between tumor and normal cells in the early steps of neuroblastoma development. Finally, we show that NPTX2 is a marker of poor prognosis for neuroblastoma patients.
journal_name
Cancer Resjournal_title
Cancer researchauthors
Bartolini A,Di Paolo D,Noghero A,Murgia D,Sementa AR,Cilli M,Pasqualini R,Arap W,Bussolino F,Ponzoni M,Pastorino F,Marchiò Sdoi
10.1158/0008-5472.CAN-15-0649subject
Has Abstractpub_date
2015-10-15 00:00:00pages
4265-71issue
20eissn
0008-5472issn
1538-7445pii
0008-5472.CAN-15-0649journal_volume
75pub_type
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