Contents lists available at ScienceDirect Tissue and Cell journal homepage: www.elsevier.com/locate/tice Dental pulp stem cells (DPSCs) increase prostate cancer cell proliferation and migration under in vitro conditions Ayşegül Doğan 1 , Selami Demirci ⁎ , Hüseyin Apdik, Ezgi Avşar Apdik, Fikrettin Şahin Department of Genetics and Bioengineering, Faculty of Engineering, Yeditepe University, Istanbul, Turkey ARTICLE INFO Keywords: DPSCs MSCs Prostate cancer Co-culture Metastasis ABSTRACT Cancer as a multistep and complicated disease is regulated by several molecular and cellular events. Cancer treatment could be managed at the early stages when the tumor is confined in the tissue. However, disseminated cancer cells metastasize to other body parts and generate new tumors resulting in mortality. Mesenchymal stem cells (MSCs) are found in different body parts and helps adult tissue regeneration. The role of MSCs in cancer progression has emerged as one of the important aspects in cancer biology and is the aim of interest in recent years. In the current study, effects of Dental Pulp Stem Cells (DPSCs) on PC-3 prostate cancer cell proliferation and migration were conducted by cell proliferation, apoptosis, gene expression and cell migration analysis in vitro. Condition medium (CM) obtained from DPSCs increased cell proliferation of PC-3 cells and decreased apoptosis. Either administration of CM or trans well co-culture of DPSCs increased cell migration in scratch assay, confirmed by gene expression analysis of migratory genes including fibronectin, laminin and collagen type I (Col I). Furthermore, DPSCs participated in a self-organized structure with PC-3 cells in co-culture conditions. Overall, results indicated that DPSCs could promote PC-3 cancer cell proliferation and metastasis in co-culture conditions in vitro. 1. Introduction Mesenchymal stem cells (MSCs) have been isolated from different body parts including bone marrow, adipose tissue, muscle or dental pulp (da Silva Meirelles et al., 2006). These cells are classified as multipotent cells thanks to their differentiation capacity into various kinds of cells such as osteoblasts, chondrocytes and adipocytes (Liu et al., 2009). The exact role of MSC in tumor metastasis and interactions have not been fully understood yet in some points regarding whether these cells contribute to the tumor progression or inhibits tumor growth (Gomes 2013). Dual interaction of MSCs and cancer cells has been re- ported in the literature in many studies. Researches clearly showed that MSCs could attract cancer cells to a desirable environment or MSCs turns to a cancer associated fibroblast phenotype and moves to tumor site to promote growth and survival (Bergfeld and DeClerck, 2010; Klopp et al., 2011). Although MSCs are not tumorigenic in in vitro adherent culture conditions, they could support tumor progression by modulating the microenvironment and epithelial to mesenchymal transition (EMT) process in vivo (Ljujic et al., 2013). MSCs recruiting to the tumor site initiate the EMT and metastasis which directly lead to the formation of cancer-initiating stem cells (CSCs) and thus, tumor progression (Kudo- Saito 2015; Yang et al., 2013). MSCs integrate into tumor tissue, sti- mulate cell migration, growth, angiogenesis and metastasis through paracrine signaling between MSCs and cancer cells (Daverey et al., 2015). The cancer-MSC interaction is complex and mediated by sig- naling molecules secreted from MSCs such as CCL5 (RANTES) and IL-6 which regulate apoptosis, metastasis, cell proliferation and tumor growth (Bergfeld and DeClerck, 2010; Torsvik and Bjerkvig, 2013). In a previous study, adipose derived MSCs (AMSCs) induce re- sistance in breast cancer cells by activating PI3 K/AKT pathway and promotes cancer cell migration (Daverey et al., 2015). Similar results were obtained in a colon cancer and AMSCs co-culture study and paracrine factors secreted from AMSCs in turn increase in metastatic capacity of colon cancer cells (Chen et al., 2015). It has been demon- strated that bone marrow MSCs (BMMSCs) increased cancer cell me- tastasis in a xenograft breast cancer model,when mixed with cancer cells and injected to animals (Karnoub et al., 2007). Liu et al. showed that BMMSCs when transplanted to NOD/SCID mice supported CSC population in breast cancer by regulating cytokine signaling including IL-6 and CXCL7 (Liu et al., 2011). In another study, contribution of BMMSCs to prostate cancer metastasis by CCL5 and androgen receptor http://dx.doi.org/10.1016/j.tice.2017.10.003 Received 29 August 2017; Received in revised form 13 October 2017; Accepted 13 October 2017 ⁎ Corresponding author at: Present address: National Heart, Lung, and Blood Institute (NHLBI), NIH, Bethesda, Maryland, United States. 1 Present address: National Cancer Institute, CDBL, NIH, Frederıck, Maryland, United States. E-mail addresses: selami.demirci@nih.gov, selamidemirci@hotmail.com (S. Demirci). Tissue and Cell xxx (xxxx) xxx–xxx 0040-8166/ Published by Elsevier Ltd. Please cite this article as: Doğan, A., Tissue and Cell (2017), http://dx.doi.org/10.1016/j.tice.2017.10.003