# Bone Marrow Mesenchymal Stem Cells Promote Ovarian Cancer Cell Proliferation via Cytokine Interactions

**Authors:** Kai-Hung Wang, Yu-Hsun Chang, Dah-Ching Ding

PMC · DOI: 10.3390/ijms25126746 · International Journal of Molecular Sciences · 2024-06-19

## TL;DR

Bone marrow stem cells help ovarian cancer cells grow by releasing cytokines, which could lead to new treatment strategies.

## Contribution

This study reveals how bone marrow mesenchymal stem cells influence ovarian cancer progression through cytokine signaling.

## Key findings

- BMSCs enhance ovarian cancer cell migration, invasion, and colony formation via conditioned medium.
- BMSCs increase tumor growth in mice and activate p38 MAPK and GSK-3β pathways in cancer cells.
- BMSCs upregulate cytokines like MCP-1 and IL-6, which may mediate cancer cell proliferation.

## Abstract

Bone marrow mesenchymal stem cells (BMSCs) are key players in promoting ovarian cancer cell proliferation, orchestrated by the dynamic interplay between cytokines and their interactions with immune cells; however, the intricate crosstalk among BMSCs and cytokines has not yet been elucidated. Here, we aimed to investigate interactions between BMSCs and ovarian cancer cells. We established BMSCs with a characterized morphology, surface marker expression, and tri-lineage differentiation potential. Ovarian cancer cells (SKOV3) cultured with conditioned medium from BMSCs showed increased migration, invasion, and colony formation, indicating the role of the tumor microenvironment in influencing cancer cell behavior. BMSCs promoted SKOV3 tumorigenesis in nonobese diabetic/severe combined immunodeficiency mice, increasing tumor growth. The co-injection of BMSCs increased the phosphorylation of p38 MAPK and GSK-3β in SKOV3 tumors. Co-culturing SKOV3 cells with BMSCs led to an increase in the expression of cytokines, especially MCP-1 and IL-6. These findings highlight the influence of BMSCs on ovarian cancer cell behavior and the potential involvement of specific cytokines in mediating these effects. Understanding these mechanisms will highlight potential therapeutic avenues that may halt ovarian cancer progression.

## Linked entities

- **Genes:** P38mapk (p38 map kinase) [NCBI Gene 692545], GSK3B (glycogen synthase kinase 3 beta) [NCBI Gene 2932], CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347], IL6 (interleukin 6) [NCBI Gene 3569]
- **Diseases:** ovarian cancer (MONDO:0005140)
- **Species:** Mus musculus (taxon 10090)

## Full-text entities

- **Genes:** GSK3B (glycogen synthase kinase 3 beta) [NCBI Gene 2932], IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, CCL2 (C-C motif chemokine ligand 2) [NCBI Gene 6347] {aka GDCF-2, HC11, HSMCR30, MCAF, MCP-1, MCP1}
- **Diseases:** cancer (MESH:D009369), diabetic (MESH:D003920), Ovarian Cancer (MESH:D010051), severe combined immunodeficiency (MESH:D016511), tumorigenesis (MESH:D063646)
- **Species:** Mus musculus (house mouse, species) [taxon 10090]
- **Cell lines:** SKOV3 — Homo sapiens (Human), Ovarian serous cystadenocarcinoma, Cancer cell line (CVCL_0532)

## Full text

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## Figures

8 figures with captions in the complete paper: https://tomesphere.com/paper/PMC11203416/full.md

## References

63 references — full list in the complete paper: https://tomesphere.com/paper/PMC11203416/full.md

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Source: https://tomesphere.com/paper/PMC11203416