Next Article in Journal
Hypersialylation in Cancer: Modulation of Inflammation and Therapeutic Opportunities
Previous Article in Journal
Oncolytic Reovirus and Immune Checkpoint Inhibition as a Novel Immunotherapeutic Strategy for Breast Cancer
Open AccessArticle

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

1
Department of Laboratory Medicine and Pathology, University of Alberta, Edmonton, AB T6G 2R3, Canada
2
Faculty of Pharmacy, Tabriz University of Medical Science, Tabriz P.O.Box 51664-14766, East Azerbaijan Province, Iran
3
Department of Oncology, University of Alberta, Edmonton, AB T6G2R7, Canada
4
Department of Medicine, University of Alberta, Edmonton, AB T6G2G3, Canada
5
Faculty of Pharmacy and Pharmaceutical Sciences, University of Alberta, Edmonton, AB T6G2H7, Canada
*
Author to whom correspondence should be addressed.
A.A. is now with the Department of Clinical Laboratory Sciences, College of Applied Medical Sciences, Taibah University, Medina P.O.Box 334, Saudi Arabia.
Cancers 2018, 10(6), 206; https://doi.org/10.3390/cancers10060206
Received: 25 April 2018 / Revised: 14 June 2018 / Accepted: 14 June 2018 / Published: 16 June 2018
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 tumor types, 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 (phospho-STAT3 or pSTAT3), which was 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 3D culture can generate results that are more representative of the disease. View Full-Text
Keywords: 3D culture; multiple myeloma; STAT; bortezomib; CETSA; Stattic 3D culture; multiple myeloma; STAT; bortezomib; CETSA; Stattic
Show Figures

Figure 1

MDPI and ACS Style

Huang, Y.-H.; 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. Cancers 2018, 10, 206.

Show more citation formats Show less citations formats
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map

1
Back to TopTop