Cancers, Vol. 12, Pages 440: Bone Marrow Stromal Cell-Derived IL-8 Upregulates PVR Expression on Multiple Myeloma Cells via NF-kB Transcription Factor

Cancers, Vol. 12, Pages 440: Bone Marrow Stromal Cell-Derived IL-8 Upregulates PVR Expression on Multiple Myeloma Cells via NF-kB Transcription Factor Cancers doi: 10.3390/cancers12020440 Authors: Abdelilah Mekhloufi Andrea Kosta Helena Stabile Rosa Molfetta Alessandra Zingoni Alessandra Soriani Marco Cippitelli Rossella Paolini Angela Gismondi Maria Rosaria Ricciardi Maria Teresa Petrucci Laura Masuelli Giulio Caracciolo Sara Palchetti Angela Santoni Cinzia Fionda Bone marrow stromal cells (BMSCs) strongly contribute to multiple myeloma (MM) progression, promoting the survival and growth of malignant plasma cells (PCs). However, the possible impact of these cells on the immune-mediated recognition of MM cells remains largely unknown. DNAM-1 activating receptor plays a prominent role in NK cell anti-MM response engaging the ligands poliovirus receptor (PVR) and nectin-2 on malignant PCs. Here, we analysed the role of MM patient-derived BMSCs in the regulation of PVR expression. We found that BMSCs enhance PVR surface expression on MM cells and promote their NK cell-mediated recognition. PVR upregulation occurs at transcriptional level and involves NF-kB transcription factor activation by BMSC-derived soluble factors. Indeed, overexpression of a dominant-negative mutant of IKBα blocked PVR upregulation. IL-8 plays a prominent role in these mechanisms since blockade of CXCR1/2 receptors as well as depletion of the cytokine via...
Source: Cancers - Category: Cancer & Oncology Authors: Tags: Article Source Type: research