title: Tumour-associated macrophages influence canine mammary cancer stem-like cells enhancing their pro-angiogenic properties.
abstract: Cancer stem-like cells as cells with ability to self-renewal and potential to differentiate into various types of cells are known to be responsible for tumour initiation, recurrence and drug resistance. Hence a comprehensive research is concentrated on discovering cancer stem-like cells biology and interdependence between them and other cells. The aim of our study was to evaluate the impact of macrophages on cancer stem-like cells in canine mammary carcinomas. As recent studies indicated presence of macrophages in cancer environment stimulates cancer cells into more motile and invasive cells by acquisition of macrophage phenotypes. From two canine mammary tumour cell lines, CMT-U27 and P114 cancer stem-like cells were stained with Sca1, CD44 and EpCAM monoclonal antibodies and isolated. Those cells were next co-cultured with macrophages for 5 days and used for further experiments. Canine Gene Expression Microarray revealed 29 different expressed transcripts in cancer stem-like cells co-cultured with macrophages compared to those in mono-culture. Up-regulation of C-C motif chemokine 2 was considered as the most interesting for further investigation. Additionally, those cells showed overexpression of genes involved in non-canonical Wnt pathway. The results of 3D tubule formation in endothelial cells induced by cancer stem-like cells co-cultured with macrophages compared to cancer stem-like cells from mono-cultures and with addition of Recombinant Canine CCL2/MCP-1 revealed the same stimulating effect. Based on those results we can conclude that macrophages have an impact on cancer stem-like cells increasing secretion of pro-angiogenic factors.
authors: Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland.
authors: A
authors: A
authors: Rybicka
authors: Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland.
authors: C
authors: C
authors: Eyileten
authors: Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland.
authors: B
authors: B
authors: Taciak
authors: Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland.
authors: J
authors: J
authors: Mucha
authors: Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland.
authors: K
authors: K
authors: Majchrzak
authors: Swedish University of Agricultural Sciences, Department of Anatomy, Physiology and Biochemistry, Uppsala, Sweden.
authors: E
authors: E
authors: Hellmen
authors: Department of Physiological Sciences, Faculty of Veterinary Medicine, Warsaw University of Life Sciences, Warsaw, Poland. magdalena_krol@sggw.pl.
authors: M
authors: M
authors: Krol
mesh_terms: D000818:Animals; D045744:Cell Line, Tumor; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000235:genetics / Q000378:metabolism*; D018920:Coculture Techniques; D004285:Dogs; D015972:Gene Expression Regulation, Neoplastic; D061307:Human Umbilical Vein Endothelial Cells / Q000378:metabolism; D006801:Humans; D008264:Macrophages / Q000378:metabolism*; D015674:Mammary Neoplasms, Animal / Q000378:metabolism / Q000473:pathology*; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D009389:Neovascularization, Pathologic / Q000235:genetics; D060449:Wnt Signaling Pathway
chemical_list: D018932:Chemokine CCL2