Abstract
Mesenchymal stem cells have been widely implicated in tumour development and metastases. Moving from the use of two-dimensional (2D) models to three-dimensional (3D) to investigate this relationship is critical to facilitate more applicable and relevant research on the tumour microenvironment. We investigated the effects of altering glucose concentration and the source of foetal bovine serum (FBS) on the growth of two breast cancer cell lines (T47D and MDA-MB-231) and human bone marrow-derived mesenchymal stem cells (hBM-MSCs) to determine successful conditions to enable their co-culture in 3D tumour spheroid models. Subsequently, these 3D multi-cellular tumour spheroids were used to investigate the effect of hBM-MSCs on breast cancer cell invasiveness. Findings presented herein show that serum source had a statistically significant effect on two thirds of the growth parameters measured across all three cell lines, whereas glucose only had a statistically significant effect on 6%. It was determined that the optimum growth media composition for the co-culture of 3D hBM-MSCs and breast cancer cell line spheroids was 1 g/L glucose DMEM supplemented with 10% FBS from source A. Subsequent results demonstrated that co-culture of hBM-MSCs and MDA-MB-231 cells dramatically reduced invasiveness of both cell lines (F(1,4) = 71.465, p = 0.001) when embedded into a matrix comprising of growth-factor reduced base membrane extract (BME) and collagen.
Highlights
IntroductionHuman mesenchymal stem cells (hMSCs) are multi-potent, non-haematopoietic cells that are plastic-adherent and can self-renew with the ability to differentiate into multiple mesenchymal lineages (osteoblasts, adipocytes, and chondrocytes)
Human mesenchymal stem cells are multi-potent, non-haematopoietic cells that are plastic-adherent and can self-renew with the ability to differentiate into multiple mesenchymal lineages
This study focused on altering serum source and glucose concentrations to determine successful co-culture conditions for two breast cancer cell lines (T47D and MDA-MB-231) with human bone marrow-derived mesenchymal stem cells, such that the interactions between these cell types could be assessed using 3D tumour spheroids
Summary
Human mesenchymal stem cells (hMSCs) are multi-potent, non-haematopoietic cells that are plastic-adherent and can self-renew with the ability to differentiate into multiple mesenchymal lineages (osteoblasts, adipocytes, and chondrocytes). HMSCs have been implicated in tumour growth and progression in several ways They have been found to play a role in the promotion of the epithelial to mesenchymal transition (EMT), a key biological process that can promote metastasis and alter the invasiveness and aggressiveness of cancer cells [2]. HMSCs can interact with tumour cells, directly and indirectly, via cell–cell interactions and paracrine signalling, resulting in altered proliferation, metabolic activity, and mobility of breast cancer cells [3,4,5,6] They may play a critical role in extracellular matrix (ECM) remodelling, again altering the invasive tendencies of cancer cells [7]. Studies have shown that hMSCs can inhibit angiogenesis and stimulate apoptosis [8], and several reviews of the topic effectively collate the evidence for the tumour suppressive effects of hMSCs [2,9,10]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
