Identification of 4Ig-B7-H3 As a Neuroblastoma-associated Molecule That Exerts a Protective Role from an NK Cell-mediated Lysis

Overview

Journal Proc Natl Acad Sci U S A

Specialty Science

Date 2004 Aug 18

PMID 15314238

Citations 149

Authors

Roberta Castriconi

Alessandra Dondero

Raffaella Augugliaro

Claudia Cantoni

Barbara Carnemolla

Angela Rita Sementa

Francesca Negri

Romana Conte

Maria Valeria Corrias

Lorenzo Moretta

Alessandro Moretta

Cristina Bottino

Affiliations

Soon will be listed here.

Abstract

In this study, in an attempt to identify neuroblastoma-associated surface antigens, we generated mAbs against the ACN neuroblastoma cell line. A mAb was selected (5B14) that reacted with all neuroblastoma cell lines analyzed and allowed detection of tumor cell infiltrates in bone marrow aspirates from neuroblastoma patients. In cytofluorimetric analysis, unlike anti-disialoganglioside mAb, 5B14 mAb did not display reactivity with normal bone marrow hematopoietic cell precursors, thus representing a highly specific marker for identifying neuroblastoma cells. Molecular analysis revealed that the 5B14 mAb-reactive surface glycoprotein corresponded to the recently identified 4Ig-B7-H3 molecule. Remarkably, mAb-mediated masking of the 4Ig-B7-H3 molecule on cell transfectants or on freshly isolated neuroblastoma cells resulted in enhancement of natural killer-mediated lysis of these target cells. These data suggest that 4Ig-B7-H3 molecules expressed at the tumor cell surface can exert a protective role from natural killer-mediated lysis by interacting with a still undefined inhibitory receptor expressed on natural killer cells.

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