Mesenchymal Stromal Cells from Female Donors Enhance Breast Cancer Cell Proliferation in vitro

Pasanen, I.; Pietilä, Mika; Lehtonen, Siri; Lehtilahti, Elisa; Hakkarainen, Tanja; Sequeiros, Roberto Blanco; Lehenkari, Petri; Kuvaja, Paula

doi:10.1159/000368556

Cited by 9 publications

(7 citation statements)

References 46 publications

(73 reference statements)

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“…Moreover, Fibroblast/cancer cell metabolic cooperation MI Koukourakis et al mesenchymal stromal cells have been shown to stimulate breast cancer cell growth, a result that, at least in part, is related to soluble factors excreted by the mesenchymal cells. 15 Partial silencing of PDH in fibroblasts did not affect the stimulatory effect of cancer cells on fibroblast cell proliferation. This, however, was shown to be a result of abrogation of the silencing effect by the lactate produced by cancer cells (lactate induces PDH in fibroblasts treated with siPDH).…”

Section: Discussionmentioning

confidence: 94%

Metabolic cooperation between co-cultured lung cancer cells and lung fibroblasts

Koukourakis

Kalamida

Mitrakas

et al. 2017

Laboratory Investigation

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Cooperation of cancer cells with stromal cells, such as cancer-associated fibroblasts (CAFs), has been revealed as a mechanism sustaining cancer cell survival and growth. In the current study, we focus on the metabolic interactions of MRC5 lung fibroblasts with lung cancer cells (A549 and H1299) using co-culture experiments and studying changes of the metabolic protein expression profile and of their growth and migration abilities. Using western blotting, confocal microscopy and RT-PCR, we observed that in co-cultures MRC5 respond by upregulating pyruvate dehydrogenase (PDH) and the monocarboxylate transporter MCT1. In contrast, cancer cells increase the expression of glucose transporters (GLUT1), LDH5, PDH kinase and the levels of phosphorylated/inactivated pPDH. H1299 cells growing in the same culture medium with fibroblasts exhibit a 'metastasis-like' phenomenon by forming nests within the fibroblast area. LDH5 and pPDH were drastically upregulated in these nests. The growth rate of both MRC5 and cancer cells increased in co-cultures. Suppression of LDHA or PDK1 in cancer cells abrogates the stimulatory signal from cancer cells to fibroblasts. Incubation of MRC5 fibroblasts with lactate resulted in an increase of LDHB and of PDH expression. Silencing of PDH gene in fibroblasts, or silencing of PDK1 or LDHA gene in tumor cells, impedes cancer cell's migration ability. Overall, a metabolic cooperation between lung cancer cells and fibroblasts has been confirmed in the context of direct Warburg effect, thus the fibroblasts reinforce aerobic metabolism to support the intensified anaerobic glycolytic pathways exploited by cancer cells.

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Section: Discussionmentioning

confidence: 94%

Metabolic cooperation between co-cultured lung cancer cells and lung fibroblasts

Koukourakis

Kalamida

Mitrakas

et al. 2017

Laboratory Investigation

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“…These discs contain all of the cell types and bone matrix that are involved in breast cancer colonisation and growth in this environment. Many in vitro models have tried to recapitulate these interactions between bone cells and tumour cells including co-culture of breast cancer cells with fibroblasts [22,23], mesenchymal stromal cells [24] osteoclasts [25], osteoblasts or a mixture of these cell types [26]. When cultured on plastic these models lack the 3D space that is critical in determining cancer cell function (reviewed in [27]).…”

Section: Tumour Cells In Moving Culturementioning

confidence: 99%

Human breast cancer bone metastasis in vitro and in vivo: a novel 3D model system for studies of tumour cell-bone cell interactions

Holen

Nutter

Wilkinson

et al. 2015

Clin Exp Metastasis

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Bone is established as the preferred site of breast cancer metastasis. However, the precise mechanisms responsible for this preference remain unidentified. In order to improve outcome for patients with advanced breast cancer and skeletal involvement, we need to better understand how this process is initiated and regulated. As bone metastasis cannot be easily studied in patients, researchers have to date mainly relied on in vivo xenograft models. A major limitation of these is that they do not contain a human bone microenvironment, increasingly considered to be an important component of metastases. In order to address this shortcoming, we have developed a novel humanised bone model, where 1 × 10(5) luciferase-expressing MDA-MB-231 or T47D human breast tumour cells are seeded on viable human subchaodral bone discs in vitro. These discs contain functional osteoclasts 2-weeks after in vitro culture and positive staining for calcine 1-week after culture demonstrating active bone resorption/formation. In vitro inoculation of MDA-MB-231 or T47D cells colonised human bone cores and remained viable for <4 weeks, however, use of matrigel to enhance adhesion or a moving platform to increase diffusion of nutrients provided no additional advantage. Following colonisation by the tumour cells, bone discs pre-seeded with MDA-MB-231 cells were implanted subcutaneously into NOD SCID mice, and tumour growth monitored using in vivo imaging for up to 6 weeks. Tumour growth progressed in human bone discs in 80 % of the animals mimicking the later stages of human bone metastasis. Immunohistochemical and PCR analysis revealed that growing MDA-MB-231 cells in human bone resulted in these cells acquiring a molecular phenotype previously associated with breast cancer bone metastases. MDA-MB-231 cells grown in human bone discs showed increased expression of IL-1B, HRAS and MMP9 and decreased expression of S100A4, whereas, DKK2 and FN1 were unaltered compared with the same cells grown in mammary fat pads of mice not implanted with human bone discs.

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“… [ 25 ] Bone Marrow M:7 F:12 Breast cancer cells proliferate increasingly when MSCs from female donors are involved. [ 31 ] Bone Marrow M:6 F:3 Female BM-MSCs’ sphingolipidome consisted of 88.35% ceramide, and 10.18% sphingomyelin. On the other hand, male BM-MSCs’ sphingolipidome included 54% ceramide, and 44.53% sphingomyelin.…”

Section: The Impact Of Donor Sex On Msc Heterogeneity and Potencymentioning

confidence: 99%

The potency of mesenchymal stem/stromal cells: does donor sex matter?

Maged,

Abdelsamed,

Wang

et al. 2024

Stem Cell Res Ther

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Mesenchymal stem/stromal cells (MSCs) are a promising therapeutic tool in cell therapy and tissue engineering because of their multi-lineage differentiation capacity, immunomodulatory effects, and tissue protective potential. To achieve optimal results as a therapeutic tool, factors affecting MSC potency, including but not limited to cell source, donor age, and cell batch, have been investigated. Although the sex of the donor has been attributed as a potential factor that can influence MSC potency and efficacy, the impact of donor sex on MSC characteristics has not been carefully investigated. In this review, we summarize published studies demonstrating donor-sex-related MSC heterogeneity and emphasize the importance of disclosing donor sex as a key factor affecting MSC potency in cell therapy.

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Mesenchymal Stromal Cells from Female Donors Enhance Breast Cancer Cell Proliferation in vitro

Cited by 9 publications

References 46 publications

Metabolic cooperation between co-cultured lung cancer cells and lung fibroblasts

Metabolic cooperation between co-cultured lung cancer cells and lung fibroblasts

Human breast cancer bone metastasis in vitro and in vivo: a novel 3D model system for studies of tumour cell-bone cell interactions

The potency of mesenchymal stem/stromal cells: does donor sex matter?

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