title: Mesenchymal stem cells from primary breast cancer tissue promote cancer proliferation and enhance mammosphere formation partially via EGF/EGFR/Akt pathway.
abstract: Mesenchymal stem cells (MSCs) play a critical role in promoting cancer progression. However, it is not clear whether MSCs are located in breast cancer tissues and correlated with tumor proliferation. The aim of this study was to investigate the presence of MSCs in breast cancer tissues and evaluate their interactions with cancer cells. We successfully isolated and identified MSCs from primary breast cancer tissues. Breast cancer-associated MSCs (BC-MSCs) showed homogenous immunophenotype, and possessed tri-lineage differentiation potential (osteoblast, adipocyte, and chondrocyte). When co-transplanted with cancer cells in a xenograft model in vivo, BC-MSCs significantly increased the volume and weight of tumors. We observed that BC-MSCs stimulated mammosphere formation in the transwell co-culture system in vitro. This effect was significantly suppressed by the EGF receptor inhibitor. We verified that BC-MSCs could secrete EGF and activate cancer cell's EGF receptors. Furthermore, our data showed that EGF derived from BC-MSCs could promote mammosphere formation via the PI3K/Akt signaling pathway. Our results confirmed the presence of MSC in primary breast cancer tissues, and they could provide a favorable microenvironment for tumor cell growth in vivo, partially enhance mammosphere formation via the EGF/EGFR/Akt pathway.
authors.affiliation: Stem Cell and Regenerative Medicine Lab, Beijing Institute of Transfusion Medicine, 27 Taiping Road, Beijing 100850, China.
authors.forename: Xin-long
authors.initials: XL
authors.lastname: Yan
authors.forename: Chun-jiang
authors.initials: CJ
authors.lastname: Fu
authors.forename: Lin
authors.initials: L
authors.lastname: Chen
authors.forename: Jin-hua
authors.initials: JH
authors.lastname: Qin
authors.forename: Quan
authors.initials: Q
authors.lastname: Zeng
authors.forename: Hong-feng
authors.initials: HF
authors.lastname: Yuan
authors.forename: Xue
authors.initials: X
authors.lastname: Nan
authors.forename: Hai-xu
authors.initials: HX
authors.lastname: Chen
authors.forename: Jun-nian
authors.initials: JN
authors.lastname: Zhou
authors.forename: Yan-li
authors.initials: YL
authors.lastname: Lin
authors.forename: Xiao-mei
authors.initials: XM
authors.lastname: Zhang
authors.forename: Cheng-ze
authors.initials: CZ
authors.lastname: Yu
authors.forename: Wen
authors.initials: W
authors.lastname: Yue
authors.forename: Xue-tao
authors.initials: XT
authors.lastname: Pei
mesh_terms: D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D001943:Breast Neoplasms / Q000473:pathology*; D018270:Carcinoma, Ductal, Breast / Q000473:pathology*; D002454:Cell Differentiation; D049109:Cell Proliferation; D048430:Cell Shape; D018920:Coculture Techniques; D004815:Epidermal Growth Factor / Q000378:metabolism / Q000502:physiology*; D066246:ErbB Receptors / Q000378:metabolism; D005260:Female; D006801:Humans; D059630:Mesenchymal Stem Cells / Q000378:metabolism*; D051379:Mice; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D014411:Neoplastic Stem Cells / Q000378:metabolism*; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D015398:Signal Transduction; D018874:Spheroids, Cellular / Q000378:metabolism*; D047368:Tumor Burden; D014407:Tumor Cells, Cultured
chemical_list: D000943:Antigens, Differentiation; D004815:Epidermal Growth Factor; D019869:Phosphatidylinositol 3-Kinases; D066246:ErbB Receptors; D051057:Proto-Oncogene Proteins c-akt