Multiple myeloma and bone marrow mesenchymal stem cells’ crosstalk: Effect on translation initiation

Oshrat Attar-Schneider, Victoria Zismanov, Mahmoud Dabbah, Shelly Tartakover-Matalon, Liat Drucker*, Michael Lishner

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

15 Scopus citations

Abstract

Multiple myeloma (MM) malignant plasma cells reside in the bone marrow (BM) and convert it into a specialized pre-neoplastic niche that promotes the proliferation and survival of the cancer cells. BM resident mesenchymal stem cells (BM-MSCs) are altered in MM and in vitro studies indicate their transformation by MM proximity is within hours. The response time frame suggested that protein translation may be implicated. Thus, we assembled a co-culture model of MM cell lines with MSCs from normal donors (ND) and MM patients to test our hypothesis. The cell lines (U266, ARP-1) and BM-MSCs (ND, MM) were harvested separately after 72 h of co-culture and assayed for proliferation, death, levels of major translation initiation factors (eIF4E, eIF4GI), their targets, and regulators. Significant changes were observed: BM-MSCs (ND and MM) co-cultured with MM cell lines displayed elevated proliferation and death as well as increased expression/activity of eIF4E/eIF4GI; MM cell lines co-cultured with MM-MSCs also displayed higher proliferation and death rates coupled with augmented translation initiation factors; in contrast, MM cell lines co-cultured with ND-MSCs did not display elevated proliferation only death and had no changes in eIF4GI levels/activity. eIF4E expression was increased in one of the cell lines. Our study demonstrates that there is direct dialogue between the MM and BM-MSCs populations that includes translation initiation manipulation and critically affects cell fate. Future research should be aimed at identifying therapeutic targets that may be used to minimize the collateral damage to the cancer microenvironment and limit its recruitment into the malignant process.

Original languageEnglish
Pages (from-to)1343-1354
Number of pages12
JournalMolecular Carcinogenesis
Volume55
Issue number9
DOIs
StatePublished - 1 Sep 2016

Funding

FundersFunder number
Israel Cancer Research Fund0601245231/2
Israel Cancer Association USA
Israel Cancer Association0601240181
Tel Aviv University

    Keywords

    • cancer microenvironment
    • eIF4E
    • eIF4GI
    • mesenchymal stem cells
    • multiple myeloma
    • translation initiation

    Fingerprint

    Dive into the research topics of 'Multiple myeloma and bone marrow mesenchymal stem cells’ crosstalk: Effect on translation initiation'. Together they form a unique fingerprint.

    Cite this