Cancer stem cell (CSC) identification relies on transplantation assays of cell subpopulations sorted from fresh tumor samples. Here, we attempt to bypass limitations of abundant tumor source and predetermined immune selection by in vivo propagating patient-derived xenografts (PDX) from human malignant rhabdoid tumor (MRT), a rare and lethal pediatric neoplasm, to an advanced state in which most cells behave as CSCs. Stemness is then probed by comparative transcriptomics of serial PDXs generating a gene signature of epithelial to mesenchymal transition, invasion/motility, metastasis, and self-renewal, pinpointing putative MRT CSC markers. The relevance of these putative CSC molecules is analyzed by sorting tumorigenic fractions from early-passaged PDX according to one such molecule, deciphering expression in archived primary tumors, and testing the effects of CSC molecule inhibition on MRT growth. Using this platform, we identify ALDH1 and lysyl oxidase (LOX) as relevant targets and provide a larger framework for target and drug discovery in rare pediatric cancers.
Download full-text PDF |
Source |
|---|---|
| http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6135722 | PMC |
| http://dx.doi.org/10.1016/j.stemcr.2018.07.010 | DOI Listing |
Publication Analysis
Top Keywords
Similar Publications
Recent research progress on microRNAs from mesenchymal stem cell-derived exosomes for tumor therapy: A review.
J Cancer Res Ther
December 2024
Department of Pathology, The First Affiliated Hospital of Shandong First Medical University and Shandong Provincial Qianfoshan Hospital, Shandong Medicine and Health Key Laboratory of Cardiac Electrophysiology and Arrhythmia, Jinan, China.
Mesenchymal stem cells (MSCs) are a class of protocells that can differentiate into various cell types and have robust replication and renewal capabilities. MSCs secrete various nutritional factors to regulate the microenvironment of tumor tissues. The mechanism by which they inhibit or promote tumor growth may be closely related to MSC-derived exosomes (MSC-Exo).
View Article and Find Full Text PDFThe role of fecal microbiota transplantation in the treatment of acute graft-versus-host disease.
J Cancer Res Ther
December 2024
Institute of Infection, Immunology and Tumor Microenvironment, Hubei Province Key Laboratory of Occupational Hazard Identification and Control, School of Medicine, Wuhan University of Science and Technology, Wuhan, China.
Allogeneic hematopoietic stem cell transplantation (allo-HSCT) is one of the most important methods for treating a wide range of hematologic malignancies and bone marrow failure diseases. However, graft-versus-host disease (GVHD), a major complication associated with this method, can seriously affect the survival and quality of life of patients. Acute GVHD (aGVHD) occurs within 100 days after transplantation, and gastrointestinal aGVHD (GI-aGVHD) is one of the leading causes of nonrecurrent death after allo-HSCT.
View Article and Find Full Text PDFTargeting BMP-1 enhances anti-tumoral effects of doxorubicin in metastatic mammary cancer: common and distinct features of TGF-β inhibition.
Breast Cancer Res Treat
January 2025
Department of Oncology, University of Torino, Via Nizza 44, 10126, Turin, Italy.
Purpose: Mammary carcinoma is comprised heterogeneous groups of cells with different metastatic potential. 4T1 mammary carcinoma cells metastasized to heart (4THM), liver (4TLM) and brain (4TBM) and demonstrate cancer-stem cell phenotype. Using these cancer cells we found thatTGF-β is the top upstream regulator of metastatic process.
View Article and Find Full Text PDFAn RNase III-processed sRNA coordinates sialic acid metabolism of during gut colonization.
Proc Natl Acad Sci U S A
January 2025
Key Laboratory of Medical Molecular Virology (Ministry of Education / National Health Commission / Chinese Academy of Medical Sciences), Shanghai Frontiers Science Center of Pathogenic Microorganisms and Infection, School of Basic Medical Sciences, Shanghai Medical College, Fudan University, Shanghai 200033, China.
Sialic acids derived from colonic mucin glycans are crucial nutrients for enteric bacterial pathogens like . The uptake and utilization of sialic acid in depend on coordinated regulons, each activated by specific metabolites at the transcriptional level. However, the mechanisms enabling crosstalk among these regulatory circuits to synchronize gene expression remain poorly understood.
View Article and Find Full Text PDFPotassium Current Signature of Neuronal/Glial Progenitors in Amniotic Fluid Stem Cells.
Cells
January 2025
Department of Chemistry, Biology and Biotechnologies, University of Perugia, Via dell'Elce di Sotto 8, 06123 Perugia, Italy.
Amniotic fluid is a complex and dynamic biological matrix that surrounds the fetus during the pregnancy. From this fluid, is possible to isolate various cell types with particular interest directed towards stem cells (AF-SCs). These cells are highly appealing due to their numerous potential applications in the field of regenerative medicine for tissues and organs as well as for treating conditions such as traumatic or ischemic injuries to the nervous system, myocardial infarction, or cancer.
View Article and Find Full Text PDFWant AI Summaries of new PubMed Abstracts delivered to your In-box?
Enter search terms and have AI summaries delivered each week - change queries or unsubscribe any time!