Type 2 Diabetes Mellitus Induced Paracrine Effects on Breast Cancer Metastasis Through Extracellular Vesicles Derived from Human Mesenchymal Stem Cells
STEM CELLS AND DEVELOPMENT
Authors: Vuong Cat Khanh; Fukushige, Mizuho; Moriguchi, Kana; Yamashita, Toshiharu; Osaka, Motoo; Hiramatsu, Yuji; Ohneda, Osamu
Abstract
Cancer metastasis is the leading cause of mortality among breast cancer patients. Type 2 diabetes mellitus (T2DM) has been suggested as a risk factor of breast cancer; however, whether or not T2DM is associated with breast tumor metastasis remains unclear. In this study, we examined the involvement of T2DM with breast cancer metastasis by a combined approach of a meta-analysis and experimental research. The results of a systematic review and meta-analysis suggested that diabetes significantly increases the risk of lymph node metastasis by 1.10-fold (P < 0.01). Consistently, our data from experimental research showed that T2DM induced paracrine effects of mesenchymal stem cells (MSCs), a key contributor to cancer progression, to stimulate metastasis of breast cancer cells (BCCs) by two independent mechanisms. First, T2DM induced the excess secretion of interleukin 6 (IL6) from MSCs, which activated the JAK/STAT3 pathway in BCCs, thus promoting the metastasis of BCCs. Second, beside the EGR-1-/IL6-dependent mechanism, T2DM altered the functions of MSC-derived extracellular vesicles (EVs), which are highly associated with the metastasis of BCCs. Our present study showed that T2DM is a risk factor for breast cancer metastasis, and MSC-derived EVs might be useful for developing a novel anti-breast cancer therapy strategy.
Biological properties of bone marrow stem cells and adipose-derived stem cells derived from T2DM rats: a comparative study
CELL AND BIOSCIENCE
Authors: Wang, Lei; Shi, Shaojie; Bai, Ruiping; Wang, Yue; Guo, Zhao; Li, Doudou
Abstract
Background Patients with type 2 diabetes mellitus (T2DM), especially those with poor glycemic control, are characterized by low bone mass and destruction of bone microstructure. Nowadays, autologous mesenchymal stem cells (auto-MSCs) have been used to repair defects and promote tissue regeneration due to handy source, low immunogenicity and self-renewing and multi-differentiating potential. However, T2DM changed the biological properties of auto-MSCs, and investigating the most suitable auto-MSCs for T2DM patients becomes a focus in tissue engineering. Results In this research, we compared the biological characteristics of adipose-derived stem cells (ASCs) and bone marrow stem cells (BMSCs) derived from T2DM rats. These results demonstrated that ASCs had a higher proliferation rate, colony-formation and cell-sheet forming ability, while BMSCs got better osteogenesis-related staining, expression of osteogenesis-related genes and proteins, and osteogenic capacity in vitro. Conclusions As it turned out, ASCs from T2DM had a higher proliferation, while BMSCs had significantly higher osteogenetic ability no matter in vitro and in vivo. Therefore, we should take into account the specific and dominated properties of MSC according to different needs to optimize the protocols and improve clinical outcomes for tissue regeneration of T2DM patients.