CD13 is a therapeutic target in human liver cancer stem cells.
Summary of "CD13 is a therapeutic target in human liver cancer stem cells."
Cancer stem cells (CSCs) are generally dormant or slowly cycling tumor cells that have the ability to reconstitute tumors. They are thought to be involved in tumor resistance to chemo/radiation therapy and tumor relapse and progression. However, neither their existence nor their identity within many cancers has been well defined. Here, we have demonstrated that CD13 is a marker for semiquiescent CSCs in human liver cancer cell lines and clinical samples and that targeting these cells might provide a way to treat this disease. CD13+ cells predominated in the G0 phase of the cell cycle and typically formed cellular clusters in cancer foci. Following treatment, these cells survived and were enriched along the fibrous capsule where liver cancers usually relapse. Mechanistically, CD13 reduced ROS-induced DNA damage after genotoxic chemo/radiation stress and protected cells from apoptosis. In mouse xenograft models, combination of a CD13 inhibitor and the genotoxic chemotherapeutic fluorouracil (5-FU) drastically reduced tumor volume compared with either agent alone. 5-FU inhibited CD90+ proliferating CSCs, some of which produce CD13+ semiquiescent CSCs, while CD13 inhibition suppressed the self-renewing and tumor-initiating ability of dormant CSCs. Therefore, combining a CD13 inhibitor with a ROS-inducing chemo/radiation therapy may improve the treatment of liver cancer.
Affiliation
Journal Details
This article was published in the following journal.
Name: The Journal of clinical investigation
ISSN: 1558-8238
Pages:
Links
- PubMed Source: http://www.ncbi.nlm.nih.gov/pubmed/20697159
- DOI: http://dx.doi.org/10.1172/JCI42550
Medical and Biotech [MESH] Definitions
Multipotent Stem Cells
Specialized stem cells that are committed to give rise to cells that have a particular function; examples are MYOBLASTS; MYELOID PROGENITOR CELLS; and skin stem cells. (Stem Cells: A Primer [Internet]. Bethesda (MD): National Institutes of Health (US); 2000 May [cited 2002 Apr 5]. Available from: http://www.nih.gov/news/stemcell/primer.htm)
Peripheral Blood Stem Cell Transplantation
Transplantation of stem cells collected from the peripheral blood. It is a less invasive alternative to direct marrow harvesting of hematopoietic stem cells. Enrichment of stem cells in peripheral blood can be achieved by inducing mobilization of stem cells from the BONE MARROW.
Embryonal Carcinoma Stem Cells
The malignant stem cells of TERATOCARCINOMAS, which resemble pluripotent stem cells of the BLASTOCYST INNER CELL MASS. The EC cells can be grown in vitro, and experimentally induced to differentiate. They are used as a model system for studying early embryonic cell differentiation.
Lymphopoiesis
Formation of LYMPHOCYTES and PLASMA CELLS from the lymphoid stem cells which develop from the pluripotent HEMATOPOIETIC STEM CELLS in the BONE MARROW. These lymphoid stem cells differentiate into T-LYMPHOCYTES; B-LYMPHOCYTES; PLASMA CELLS; or NK-cells (KILLER CELLS, NATURAL) depending on the organ or tissues (LYMPHOID TISSUE) to which they migrate.
Hep G2 Cells
A human liver tumor cell line used to study a variety of liver-specific metabolic functions.
PubMed Articles
BACKGROUND: Recently, it has been reported that a small population of cancer stem cells (CSCs) play a role in resistance to chemotherapy and radiation therapy. We reported that CD13(+) liver CSCs surv...
Malignant fibrous histiocytoma (MFH), a high-grade, undifferentiated sarcoma, is highly aggressive, resistant to radiochemotherapy and associated with poor prognosis. There are no specific immunohisto...
Control of APN/CD13 and NEP/CD10 on sperm motility.
Aminopeptidase N (APN/CD13) and neutral endopeptidase (NEP/CD10) are enzymes present in human sperm cells and involved in regulation of sperm motility of noncapacitated spermatozoa. We investigated th...
The aim of this study was to analyse the expression of matrix metalloproteinase-2(MMP-2), matrix metalloproteinase-9 (MMP-9) and aminopeptidase APN/CD13 in breast carcinoma samples, and their possible...
BACKGROUND & AIMS:: Chemotherapy is used to treat unresectable liver cancer with marginal efficacy; this might result from hepatic cancer cells with stem-cell and chemoresistant features. Gene express...
Clinical Trials
The results of this study may or may not establish useful baseline data, which will help us understand how bone marrow derived adult liver stem cells behave in normal healthy adults/volunt...
This is a prospective dose escalation study of the administration of adult human stem cells in patients with end stage liver failure. Successive groups of two patients will receive ascendi...
Dose Finding Study to Assess Safety and Efficacy of Stem Cells in Liver Cirrhosis
This study will evaluate the safety and efficacy of mesenchymal stem cells in patients with cirrhosis of liver. Stem cells will be injected into the hepatic artery. Improvement in various...
Adult Stem Cell Therapy in Liver Insufficiency
In order to determine the clinical application potential of adult stem cells we propose to investigate the safety and toxicity of infusing adult stem cells in the hepatic artery or portal...
The methods for separation of mesenchymal stem cell were established in 2001. These cells can differentiate to osteocytes, hepatocytes, chondrocytes, myocytes and etc,. In this study the i...
