Tumor-associated mesenchymal stem cells in chemically-induced breast cancer in Wistar rats

Abstract

Objective: to compare the morphological and functional properties of mesenchymal stem cells from mammary tissues and chemically-induced mammary tumor tissues. material and methods. The study included 25 female Wistar rats. In 20 rats, mammary carcinoma was induced by intramammary injection of N-methyl-N-nitrosourea after estrus synchronization with chorionic gonadotropin. The control group consisted of 5 rats. Mammary carcinoma was verified histologically and immunohistochemically. To examine, whether the cells isolated from normal tissue and tumor tissue belonged to mesenchymal stem cells, FACS Canto II flow cytofluorometer was used. The functional properties of mesenchymal stem cells were evaluated in MTT assay by the level of nitric oxide production in normal and by hydrogen peroxide-induced hypoxia. The levels of prolactin, luteinizing hormone and estradiol E2 in urine were studied using solid-phase enzyme-linked immunosorbent assay. results. Chemically-induced mammary tumor according to histological and immunohistochemical studies corresponded to luminal B type breast cancer in humans. In rats that developed mammary tumors, the urine prolactin levels after synchronization of estrus were increased. In rats that did not develop tumors, the levels of prolactin and luteinizing hormone were decreased, but the levels of estradiol E2 were increased. More mesenchymal stem cells with CD45-/CD90+phenotype were obtained from the breast tumor tissue. Mesenchymal stem cells from tumor tissue showed increased proliferative potential and were more resistant to hypoxia. conclusion. Tumor- associated mesenchymal stem cells having high proliferative potential and resistance to hypoxia were obtained from chemically-induced mammary tumor tissue. Morphologic and functional differences in mesenchymal stem cells obtained from mammary breast tissue and tumor tissue require further studies.