Cell adhesion molecule CD166 drives malignant progression and osteolytic disease in multiple myeloma

Linlin Xu, Khalid Mohammad, Hao Wu, Colin Crean, Bradley Poteat, Yinghua Cheng, Angelo A. Cardoso, Christophe Machal, Helmut Hanenberg, Rafat Abonour, Melissa Kacena, John Chirgwin, Attaya Suvannasankha, Edward Srour

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

Multiple myeloma is incurable once osteolytic lesions have seeded at skeletal sites, but factors mediating this deadly pathogenic advance remain poorly understood. Here, we report evidence of a major role for the cell adhesion molecule CD166, which we discovered to be highly expressed in multiple myeloma cell lines and primary bone marrow cells from patients. CD166+ multiple myeloma cells homed more efficiently than CD166- cells to the bone marrow of engrafted immunodeficient NSG mice. CD166 silencing in multiple myeloma cells enabled longer survival, a smaller tumor burden, and less osteolytic lesions, as compared with mice bearing control cells. CD166 deficiency in multiple myeloma cell lines or CD138+ bone marrow cells from multiple myeloma patients compromised their ability to induce bone resorption in an ex vivo organ culture system. Furthermore, CD166 deficiency in multiple myeloma cells also reduced the formation of osteolytic disease in vivo after intratibial engraftment. Mechanistic investigation revealed that CD166 expression in multiple myeloma cells inhibited osteoblastogenesis of bone marrow-derived osteoblast progenitors by suppressing Runx2 gene expression. Conversely, CD166 expression in multiple myeloma cells promoted osteoclastogenesis by activating TRAF6-dependent signaling pathways in osteoclast progenitors. Overall, our results define CD166 as a pivotal director in multiple myeloma cell homing to the bone marrow and multiple myeloma progression, rationalizing its further study as a candidate therapeutic target for multiple myeloma treatment.

Original languageEnglish (US)
Pages (from-to)6901-6910
Number of pages10
JournalCancer Research
Volume76
Issue number23
DOIs
StatePublished - Dec 1 2016

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Cell Adhesion Molecules
Multiple Myeloma
Disease Progression
Bone Marrow Cells
Bone Marrow
TNF Receptor-Associated Factor 6
Cell Line
Organ Culture Techniques
Osteoclasts
Bone Resorption
Tumor Burden
Osteoblasts
Osteogenesis
Gene Expression

ASJC Scopus subject areas

  • Oncology
  • Cancer Research

Cite this

Cell adhesion molecule CD166 drives malignant progression and osteolytic disease in multiple myeloma. / Xu, Linlin; Mohammad, Khalid; Wu, Hao; Crean, Colin; Poteat, Bradley; Cheng, Yinghua; Cardoso, Angelo A.; Machal, Christophe; Hanenberg, Helmut; Abonour, Rafat; Kacena, Melissa; Chirgwin, John; Suvannasankha, Attaya; Srour, Edward.

In: Cancer Research, Vol. 76, No. 23, 01.12.2016, p. 6901-6910.

Research output: Contribution to journalArticle

Xu, Linlin ; Mohammad, Khalid ; Wu, Hao ; Crean, Colin ; Poteat, Bradley ; Cheng, Yinghua ; Cardoso, Angelo A. ; Machal, Christophe ; Hanenberg, Helmut ; Abonour, Rafat ; Kacena, Melissa ; Chirgwin, John ; Suvannasankha, Attaya ; Srour, Edward. / Cell adhesion molecule CD166 drives malignant progression and osteolytic disease in multiple myeloma. In: Cancer Research. 2016 ; Vol. 76, No. 23. pp. 6901-6910.
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