Interaction of adipose-derived mesenchymal stem cells with MCF-7 cells in vitro:a study emphasizing signaling molecule expression and transcriptional changes

Abstract

IntroductionAdipose-derived mesenchymal stem cells (ADSCs) are a heterogeneous population of adult stem cells derived from adipose tissue. ADSCs functionally differentiate into various cell lineages in a special microenvironment (Uzbas et al., 2015). ADSCs are autologous, available in sufficient quantities in most patients, and are widely used in soft tissue repair, for instance, in breast reconstruction in surgical patients (Rowan et al., 2014). However, recent papers indicate ADSCs potentially induce a tumor microenvironment and affect tumor cell biology. In mammary tissue (Muehlberg et al., 2009), resident stem cells promote breast cancer metastasis, home to the tumor site, and stimulate tumor growth not only when coinjected locally but also when injected intravenously. Kucerova et al. (2011) reported that ADSCs could stimulate proliferation of several breast cancer cells in vitro, such as MDA-MB-361, T47D, and EGFP-MCF-7. Kim et al. (2013) found that breast and abdominal adipose tissues have comparable gene expression profiles and are comparable in supporting breast cancer cell proliferation and metastasis. On the other hand, it has been previously reported that the morphology and phenotype of ADSCs are altered when cocultured with tumor cells. ADSCs (Jotzu et al., 2011) that received tumor-derived factors differentiated into carcinoma-associated fibroblast-like cells, which functionally contribute to tumor growth, invasion, and metastasis. ADSCs directly cocultured with H358 lung cancer cells differentiated into tumor stroma that play a supportive role during cancer progression (Park et al., 2013).Of note, except for the diffusible factors (cytokines, chemokine, and growth factors), cell-derived exosomes have been described as a new signal in cell-to-cell communication. Exosomes are membrane vesicles (30-100 nm) from luminal membranes of multivesicular bodies and are constitutively released upon fusion with cell membranes (Tan et al., 2016). It has been previously confirmed that ADSCs secrete exosomes (Cho et al., 2012;Lin et al., 2013), promote MCF-7 cell migration, and that exosomes from breast cancer cells convert ADSCs into myofibroblast-like cells. These results provide evidence that exosomes play a role in crosstalk between ADSCs and MCF-7 cells.