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High expression of neuropeptide Y1 receptors in ewing sarcoma tumors
Meike Körner1, Beatrice Waser, Jean Claude Reubi
1Division of Cell Biology and Experimental Cancer Research, Institute of Pathology of the University of Berne, Murtenstrasse 31, Berne, Switzerland.
Purpose:
Peptide receptors are frequently overexpressed in human tumors, allowing receptor-targeted scintigraphic imaging and therapy with radiolabeled peptide analogues. Neuropeptide Y (NPY) receptors are new candidates for these applications, based on their high expression in specific cancers. Because NPY receptors are expressed in selected sarcoma cell lines and because novel treatment options are needed for sarcomas, this study assessed the NPY receptor in primary human sarcomas.
Experimental Design:
Tumor tissues of 88 cases, including Ewing sarcoma family of tumors (ESFT), synovial sarcomas, osteosarcomas, chondrosarcomas, liposarcomas, angiosarcomas, rhabdomyosarcomas, leiomyosarcomas, and desmoid tumors, were investigated for NPY receptor protein with in vitro receptor autoradiography using (125)I-labeled NPY receptor ligands and for NPY receptor mRNA expression with in situ hybridization.
Results:
ESFT expressed the NPY receptor subtype Y1 on tumor cells in remarkably high incidence (84%) and density (mean, 5,314 dpm/mg tissue). Likewise, synovial sarcomas expressed Y1 on tumor cells in high density (mean, 7,497 dpm/mg; incidence, 40%). The remaining tumors expressed NPY receptor subtypes Y1 or Y2 at lower levels. Moreover, many of the sarcomas showed Y1 expression on intratumoral blood vessels. In situ hybridization for Y1 mRNA confirmed the autoradiography results.
Conclusions:
NPY receptors are novel molecular markers for human sarcomas. Y1 may inhibit growth of specific sarcomas, as previously shown in an in vivo mouse model of human ESFT. The high Y1 expression on tumor cells of ESFT and synovial sarcomas and on blood vessels in many other sarcomas represents an attractive basis for an in vivo tumor targeting.
Insights
Neuropeptide Y (NPY) receptors, particularly subtype Y1, are highly expressed in Ewing sarcoma family of tumors and synovial sarcomas. This discovery offers a promising avenue for targeted imaging and therapy in human sarcomas.
Area of Science:
- Oncology
- Molecular Imaging
- Receptor Biology
Background:
- Peptide receptors are frequently overexpressed in human tumors, making them targets for scintigraphic imaging and therapy.
- Neuropeptide Y (NPY) receptors are emerging candidates due to their high expression in specific cancers.
- Sarcomas represent a diverse group of cancers with a need for novel treatment strategies.
Purpose of the Study:
- To investigate the expression and potential of Neuropeptide Y (NPY) receptors as molecular markers in primary human sarcomas.
- To assess the presence of NPY receptor subtypes Y1 and Y2 in various sarcoma types.
- To evaluate the feasibility of NPY receptor-targeted therapies for sarcomas.
Main Methods:
- Analysis of 88 primary human sarcoma tumor tissues, including Ewing sarcoma family of tumors (ESFT), synovial sarcomas, and others.
- In vitro receptor autoradiography using (125)I-labeled NPY receptor ligands to detect NPY receptor protein.
- In situ hybridization to determine NPY receptor mRNA expression levels.
Main Results:
- Ewing sarcoma family of tumors (ESFT) showed high incidence (84%) and density of NPY receptor subtype Y1.
- Synovial sarcomas also exhibited high density of Y1 expression on tumor cells.
- Other sarcomas displayed lower levels of Y1 or Y2 expression, with Y1 noted on intratumoral blood vessels.
Conclusions:
- Neuropeptide Y (NPY) receptors serve as novel molecular markers for human sarcomas.
- High Y1 expression on ESFT and synovial sarcoma cells, and on blood vessels in other sarcomas, provides a basis for in vivo tumor targeting.
- NPY receptors, especially Y1, hold potential for targeted scintigraphic imaging and therapeutic applications in sarcoma treatment.
