RRC ID 72253
Author Osman A, Oze M, Afify SM, Hassan G, El-Ghlban S, Nawara HM, Fu X, Zahra MH, Seno A, Winer I, Salomon DS, Seno M.
Title Tumor-associated macrophages derived from cancer stem cells.
Journal Acta Histochem
Abstract Macrophages are the most abundant immune cells in the microenvironment of solid tumors. The present study displayed histological and immunohistochemical analyses of a malignant tumor model developed from cancer stem cells (CSCs) converted from human induced pluripotent stem cells (hiPSCs) in a cancer microenvironment prepared from the conditioned medium (CM) of a pancreatic cancer cell line. We focused on the localization and the origin of tumor-associated macrophages (TAMs), To the best of our knowledge this may be the first study to suggest the potential differentiation of CSCs to TAMs. hiPSCs were converted into CSCs in the presence of CM from PK8 cells. CSCs were then transplanted in vivo and formed primary tumors. Primary cultures for these tumors were serially transplanted again to obtain secondary tumors. Secondary tumors exhibited histopathological features of malignancy. Cells derived from tumors maintained the expression of endogenous stemness markers and pancreatic CSCs markers. Simultaneously, high immunoreactivity to anti-mouse CD68, anti-human CD68, CD206 and CD11b antibodies were detected revealing that the tumor tissue derived from CSCs was enriched for macrophages which can originate from both human and mouse cells. The model of CSCs highlighted the possibility of CSCs to differentiate into TAMs.
Volume 122(8)
Pages 151628
Published 2020-12-1
DOI 10.1016/j.acthis.2020.151628
PII S0065-1281(20)30127-6
PMID 32992123
MeSH Animals Antigens, CD / genetics Antigens, CD / metabolism Antigens, Differentiation, Myelomonocytic / genetics Antigens, Differentiation, Myelomonocytic / metabolism Biomarkers / metabolism CD11b Antigen / genetics CD11b Antigen / metabolism Cell Differentiation / drug effects* Cell Line, Tumor Culture Media, Conditioned / pharmacology* Gene Expression Humans Immunohistochemistry Induced Pluripotent Stem Cells / drug effects* Induced Pluripotent Stem Cells / metabolism Induced Pluripotent Stem Cells / pathology Male Membrane Glycoproteins / genetics Membrane Glycoproteins / metabolism Mice Mice, SCID Neoplasm Transplantation Neoplastic Stem Cells / drug effects* Neoplastic Stem Cells / metabolism Neoplastic Stem Cells / pathology Pancreatic Neoplasms / genetics Pancreatic Neoplasms / metabolism Pancreatic Neoplasms / pathology Receptors, Immunologic / genetics Receptors, Immunologic / metabolism Tumor Microenvironment / genetics Tumor-Associated Macrophages / drug effects* Tumor-Associated Macrophages / metabolism Tumor-Associated Macrophages / pathology
Human and Animal Cells 409B2(HPS0076)