CD166 modulates disease progression and osteolytic disease in multiple myeloma
type: CreativeWork
description: Multiple myeloma (MM) is an incurable malignancy characterized by the proliferation of neoplastic plasma cells in the bone marrow (BM) and by multiple osteolytic lesions throughout the skeleton. We previously reported that CD166 is a functional molecule on normal hematopoietic stem cells (HSC) that plays a critical role in HSC homing and engraftment, suggesting that CD166 is involved in HSC trafficking and lodgment. CD166, a member of the immunoglobulin superfamily capable of mediating homophilic interactions, has been shown to enhance metastasis and invasion in several tumors. However, whether CD166 is involved in MM and plays a role in MM progression has not been addressed. We demonstrated that a fraction of all human MM cell lines tested and MM patients’ BM CD138+ cells express CD166. Additionally, CD166+ cells preferentially home to the BM of NSG mice. Knocking-down (KD) CD166 expression on MM cells with shRNA reduced their homing to the BM. Furthermore, in a long-term xenograft model, NSG mice inoculated with CD166KD cells showed delayed disease progression and prolonged survival compared to mice receiving mock transduced cells. To examine the potential role of CD166 in osteolytic lesions, we first used a novel Ex Vivo Organ Culture Assay (EVOCA) which creates an in vitro 3D system for the interaction of MM cells with the bone microenvironment. EVOCA data from MM cells lines as well as from primary MM patients’ CD138+ BM cells demonstrated that bone osteolytic resorption was significantly reduced when CD166 was absent on MM cells or calvarial cells. We then confirmed our ex vivo findings with intra-tibial inoculation of MM cells in vivo. Mice inoculated with CD166KD cells had significantly less osteolytic lesions. Further analysis demonstrated that CD166 expression on MM cells alters bone remodeling by inhibiting RUNX2 gene expression in osteoblast precursors and increasing RANKL to OPG ratio in osteoclast precursors. We also identified that CD166 is indispensa…
abstract: Multiple myeloma (MM) is an incurable malignancy characterized by the proliferation of neoplastic plasma cells in the bone marrow (BM) and by multiple osteolytic lesions throughout the skeleton. We previously reported that CD166 is a functional molecule on normal hematopoietic stem cells (HSC) that plays a critical role in HSC homing and engraftment, suggesting that CD166 is involved in HSC trafficking and lodgment. CD166, a member of the immunoglobulin superfamily capable of mediating homophilic interactions, has been shown to enhance metastasis and invasion in several tumors. However, whether CD166 is involved in MM and plays a role in MM progression has not been addressed. We demonstrated that a fraction of all human MM cell lines tested and MM patients’ BM CD138+ cells express CD166. Additionally, CD166+ cells preferentially home to the BM of NSG mice. Knocking-down (KD) CD166 expression on MM cells with shRNA reduced their homing to the BM. Furthermore, in a long-term xenograft model, NSG mice inoculated with CD166KD cells showed delayed disease progression and prolonged survival compared to mice receiving mock transduced cells. To examine the potential role of CD166 in osteolytic lesions, we first used a novel Ex Vivo Organ Culture Assay (EVOCA) which creates an in vitro 3D system for the interaction of MM cells with the bone microenvironment. EVOCA data from MM cells lines as well as from primary MM patients’ CD138+ BM cells demonstrated that bone osteolytic resorption was significantly reduced when CD166 was absent on MM cells or calvarial cells. We then confirmed our ex vivo findings with intra-tibial inoculation of MM cells in vivo. Mice inoculated with CD166KD cells had significantly less osteolytic lesions. Further analysis demonstrated that CD166 expression on MM cells alters bone remodeling by inhibiting RUNX2 gene expression in osteoblast precursors and increasing RANKL to OPG ratio in osteoclast precursors. We also identified that CD166 is indispensa…
author: Xu, Linlin
language: en_US
keywords: CD166, Bone disease, Multipe Myeloma, Osteoblast, Osteoclast
date published: 2016-03-16
date modified: 2026-07-24T02:42:13Z
provider: IUPUI
publisher: Networked Digital Library of Theses and Dissertations
type: WebPage
source organization: IUPUI

PropertyValue
property ID: Handle
value: https://hdl.handle.net/1805/10477

PropertyValue
property ID: DOI
value: 10.7912/C2/1742

PropertyValue
property ID: DOI
value: 10.7912/C2ZK5W