Preprint Article Version 1 Preserved in Portico This version is not peer-reviewed

Constitutive Activation of STAT3 in Myeloma Cells Cultured in a Three-Dimensional, Reconstructed Bone Marrow Model

Yung-Hsing Huang
ORCID logo ,
Ommoleila Molavi
,
Abdulraheem Alshareef
ORCID logo ,
Moinul Haque
,
Qian Wang
,
Michael P. Chu
,
Christopher P. Venner
,
Irwindeep Sandhu
,
Anthea C. Peters
,
Afsaneh Lavasanifar
,
Raymond Lai
*
Version 1 : Received: 17 March 2018 / Approved: 19 March 2018 / Online: 19 March 2018 (09:27:24 CET)
Version 2 : Received: 8 June 2018 / Approved: 8 June 2018 / Online: 8 June 2018 (13:32:11 CEST)

How to cite: Huang, Y.; Molavi, O.; Alshareef, A.; Haque, M.; Wang, Q.; Chu, M.P.; Venner, C.P.; Sandhu, I.; Peters, A.C.; Lavasanifar, A.; Lai, R. Constitutive Activation of STAT3 in Myeloma Cells Cultured in a Three-Dimensional, Reconstructed Bone Marrow Model. Preprints 2018, 2018030151. https://doi.org/10.20944/preprints201803.0151.v1 Huang, Y.; Molavi, O.; Alshareef, A.; Haque, M.; Wang, Q.; Chu, M.P.; Venner, C.P.; Sandhu, I.; Peters, A.C.; Lavasanifar, A.; Lai, R. Constitutive Activation of STAT3 in Myeloma Cells Cultured in a Three-Dimensional, Reconstructed Bone Marrow Model. Preprints 2018, 2018030151. https://doi.org/10.20944/preprints201803.0151.v1

Abstract

Malignant cells cultured in three-dimensional (3D) models have been found to be phenotypically and biochemically different from their counterparts cultured conventionally. Since most of these studies employed solid cancers, how 3D culture affects multiple myeloma (MM) cells is not well understood. Here, we compared MM cells (U266 and RPMI8226) in a 3D culture model with those in conventional culture. While the conventionally cultured cells were present in single cells or small clusters, MM-3D cells grew in large spheroids. We discovered that STAT3 was the pathway that was more activated in 3D in both cell lines. The active form of STAT3 (pSTAT3), being absent in MM cells cultured conventionally, became detectable after 1-2 days in 3D culture. This elevated pSTAT3 level was dependent on the 3D environment, since it disappeared after transferring to conventional culture. STAT3 inhibition using a pharmacological agent, Stattic, significantly decreased the cell viability of MM cells and sensitized them to bortezomib in 3D culture. Using an oligonucleotide array, we found that 3D culture significantly increased the expression of several known STAT3 downstream genes implicated in oncogenesis. Since most primary MM tumors are naturally STAT3-active, studies of MM in the 3D culture can generate results that are more representative of the disease.

Keywords

3D culture; multiple myeloma; STAT; bortezomib; CETSA; stattic

Subject

Medicine and Pharmacology, Oncology and Oncogenics

Copyright: This is an open access article distributed under the Creative Commons Attribution License which permits unrestricted use, distribution, and reproduction in any medium, provided the original work is properly cited.

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Comments (1)

Comment 1
Received: 16 June 2018
Commenter: Jone W
The commenter has declared there is no conflict of interests.
Comment: Do any cancer cell lines gain Stat3 activity in this 3D culture assay? or this is an unique case for the two MM cell lines and a very limited MM patient samples?
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