R&D Systems Tools for Cell Biology Research™ STEM CELL FOCUS: CANCER STEM CELLS Cancer Stem Cell Markers FEATURED DATA: Aminopeptidase N · BMI-1 · CD24 · CD44 · E-Cadherin · EpCam/TROP1 · ErbB2/Her2 · STRO-1 · Tumorspheres The CSC Hypothesis Like all stem cells, oncogenically trans formed cancer stem cells (CSCs) are defined by their ability for self-renewal and multi potency. The CSC hypothesis states that, although CSCs represent a rare population of cells within a tumor, their high tumorigenic capacity drives tumorigenesis. Due to their intrinsic stem cell-like properties, CSC proliferation gen- erates more CSCs and all the differentiated cell types that compose the bulk of the tumor. Differentiated cancer cells have been shown to proliferate at a faster rate than CSCs but have little tumor-initiating potential. Because CSCs exhibit increased resistance to toxic and chemical insults, this specific subpopulation of cells is believed to underlie resistance to chemotherapy and disease relapse. In fact, the CSC model suggests that all CSCs must be eradicated to eliminate a tumor and prevent its recurrence. Malignancy-specific Markers Available for: Unlike the differentiated cancer cells in a Bladder Cancer Lung Cancer tumor, CSCs are capable of forming new tumors when xenotransplanted into Breast Cancer Melanoma immunodeficient animal models. Although Colon Cancer Myeloma inconsistencies in these studies have questioned the validity of the CSC hypothesis, Gastric Cancer Osteosarcoma it is likely that variable findings result from differences in assay sensitivity and Glioma/Medulloblastoma Ovarian Cancer quantification methodology. An overriding Head & Neck Cancer Pancreatic Cancer exper imental limitation for CSC researchers is the ability to identify and isolate CSCs from Leukemia Prostate Cancer other tumor cells. To address this need, we Liver Cancer present a table of molecules identified in the current literature as markers of CSCs detected Tissue Specific Expression of Cancer Stem Cell (CSC) Markers. This illustration depicts a tumor containing a small population of CSCs. For more information and in specific malignancies. a list of products for malignancy-specific CSC markers, please visit www.RnDSystems.com/CSC. For more information, please visit: www.RnDSystems.com/CSC R&D Systems Products for Cancer Stem Cell Markers ELISAs ELISAs RECOMBINANT CELL SELECTION RECOMBINANT CELL SELECTION MOLECULE & NATURAL ANTIBODIES & DETECTION MOLECULE & NATURAL ANTIBODIES & DETECTION PROTEINS KITS & REAGENTS PROTEINS KITS & REAGENTS Bladder Cancer Stem Cell Markers Musashi-1 H (IHC, WB) CD44 H M R P H (FC, IHC, IP, WB) M (B/N, FC, IHC, WB) H Gastric Cancer Stem Cell Markers R (B/N, FC, IHC, WB) Ca (FC) CD44 H M R P H (FC, IHC, IP, WB) M (B/N, FC, IHC, WB) H CD47 H H (B/N, FC, IHC, WB) M (FC, IHC, WB) R (B/N, FC, IHC, WB) Ca (FC) Breast Cancer Stem Cell Markers DLL4 H M H (FC, IHC, WB) M (ELISA, WB) M Aldehyde H H (IHC, IP, WB) Glioma/Medulloblastoma Cancer Stem Cell Markers Dehydrogenase 1-A1/ ALDH1A1 A20/TNFAIP3 H BMI-1 H (ChIP, FC, IHC, WB) H ABCG2 H (FC, IHC) CD24 H H (FC, IHC, WB) H CD49f/Integrin α6 H (B/N, FC, IHC, IP, WB) M (B/N, FC, IHC) B (B/N, FC, IHC) CD44 H M R P H (FC, IHC, IP, WB) M (B/N, FC, IHC, WB) H R (B/N, FC, IHC, WB) Ca (FC) CD126/IL-6 Rα H M H (B/N, ELISA, FC, IHC, WB) H M M (B/N, ELISA, FC, IHC, WB) CD49f/Integrin α6 H (B/N, FC, IHC, IP, WB) M (B/N, FC, IHC) B (B/N, FC, IHC) CD171/NCAM-L1 H M H (IHC, WB) M (FC) CD126/IL-6 Rα H M H (B/N, ELISA, FC, IHC, WB) H M CX3CR1 H (FC, WB) M (FC, WB) M (B/N, ELISA, FC, IHC, WB) CXCR4 H (B/N, FC, IHC) M (B/N, FC, IHC) F (FC, IHC) H CXCR1/IL-8 RA H (B/N, FC, IHC) CX3CL1/Fractalkine H M R H (B/N, ELISA, FC, IHC, WB) M (B/N, ELISA, WB) H M R CXCR4 H (B/N, FC, IHC) M (B/N, FC, IHC) F (FC, IHC) H R (B/N, ELISA, IHC, WB) DLL4 H M H (FC, IHC, WB) M (ELISA, WB) M HIF-2α/EPAS1 H (ChIP, IHC, WB) M (IHC, WB) R (ChIP, IHC, WB) H EpCAM/TROP1 H H (ELISA, FC, IHC, WB) H H Musashi-1 H (IHC, WB) ErbB2/Her2 H H (B/N, ELISA, FC, IHC, WB) M (FC, IHC, WB) H H c-Myc H (ChIP, IHC, WB) H GLI-1 H (ChIP, IHC, WB) M (IHC, WB) H Nestin H (FC, IHC) M (FC, IHC, WB) R (FC, IHC, WB) GLI-2 H (ChIP, IHC, WB) M (IHC, WB) H Podoplanin H M H (FC, IHC, WB) M (IHC, WB) PTEN H H (FC, IHC, WB) M (FC, IHC, WB) R (FC, IHC, WB) H M R Head & Neck Cancer Stem Cell Markers Colon Cancer Stem Cell Markers ABCG2 H (FC, IHC) Aldehyde H H (IHC, IP, WB) Aldehyde H H (IHC, IP, WB) Dehydrogenase 1-A1/ Dehydrogenase 1-A1/ ALDH1A1 ALDH1A1 CD44 H M R P H (FC, IHC, IP, WB) M (B/N, FC, IHC, WB) H BMI-1 H (ChIP, FC, IHC, WB) H R (B/N, FC, IHC, WB) Ca (FC) CD44 H M R P H (FC, IHC, IP, WB) M (B/N, FC, IHC, WB) H CD26/DPPIV H M H (ELISA, FC, IHC, WB) M (ELISA, FC, IHC, IP, WB) H M R (B/N, FC, IHC, WB) Ca (FC) CD166/ALCAM H M H (B/N, ELISA, FC, WB) M (FC, IHC, WB) H M Leukemia Cancer Stem Cell Markers EpCAM/TROP1 H H (ELISA, FC, IHC, WB) H H BMI-1 H (ChIP, FC, IHC, WB) H GLI-1 H (ChIP, IHC, WB) M (IHC, WB) H CD34 H (FC, IHC) M (FC, WB) R (FC, IHC, WB) Ca (FC, WB) P (WB) Species Key: H Human M Mouse R Rat B Bovine Ca Canine CR Cotton Rat F Feline P Porcine Application Key: B/N Blocking/Neutralization ChIP Chromatin Immunoprecipitation ELISA ELISA Capture and/or Detection FC Flow Cytometry IHC Immunohistochemistry IP Immunoprecipitation WB Western blot 120 100 80 60 40 Relative Cell Number Cell Relative 20 0 100 101 102 103 104 BMI-1 EpCAM/TROP-1 in the HT-29 Human Cell Line. Epithelial Cellular Adhesion Intracellular Detection of BMI-1 by Flow Cytometry. The HeLa human cervical Aminopeptidase N in Human Liver Cancer Tissue. Aminopeptidase N/ANPEP Molecule (EpCAM/TROP1) was detected in immersion-fixed HT-29 human colon epithelial carcinoma cell line was stained with an APC-conjugated Mouse Anti- was detected in immersion-fixed paraffin-embedded sections of human liver adenocarcinoma cells using a Mouse Anti-Human EpCAM/TROP1 Monoclonal Human BMI-1 Monoclonal Antibody (Catalog # IC33341A; filled histogram) or an cancer tissue using a Sheep Anti-Human Aminopeptidase N Antigen Affinity- Antibody (Catalog # MAB960). The cells were stained using the NorthernLights™ APC-conjugated Mouse IgG2A Isotype Control Antibody (Catalog # IC003A; open purified Polyclonal Antibody (Catalog # AF3815). The tissue was stained using the 493-conjugated Donkey Anti-Mouse IgG Secondary Antibody (Catalog # NL009; histogram). Anti-Sheep HRP-DAB Cell & Tissue Staining Kit (Catalog # CTS019; brown) and green) and the nuclei were counterstained with DAPI (blue). Specific staining was counterstained with hematoxylin (blue). Specific labeling was localized to bile localized to the cell surface and the cytoplasm. canaliculi. www.RnDSystems.com/CSC For more information, please visit: www.RnDSystems.com/CSC ELISAs ELISAs RECOMBINANT CELL SELECTION RECOMBINANT CELL SELECTION MOLECULE & NATURAL ANTIBODIES & DETECTION MOLECULE & NATURAL ANTIBODIES & DETECTION PROTEINS KITS & REAGENTS PROTEINS KITS & REAGENTS CD38 H M H (FC, IHC, IP, WB) M (FC, WB) CD271/NGF R/ H M H (FC, IHC, WB) M (IHC, WB) M TNFRSF16 CD44 H M R P H (FC, IHC, IP, WB) M (B/N, FC, IHC, WB) H R (B/N, FC, IHC, WB) Ca (FC) Nestin H (FC, IHC) M (FC, IHC, WB) R (FC, IHC, WB) CD47 H H (B/N, FC, IHC, WB) M (FC, IHC, WB) Myeloma Cancer Stem Cell Markers CD96 M H (FC, WB) M (FC, WB) CD19 H (FC) CD117/SCF R/c-kit H H (B/N, ELISA, FC, IHC, WB) M (FC, IHC, WB) H CD20/MS4A1 H (FC) CD123/IL-3 Rα H M H (B/N, FC, IHC, WB) M (FC, WB) CD27/TNFRSF7 H M H (B/N, FC, IHC, WB) M (ELISA, FC, WB) M GLI-1 H (ChIP, IHC, WB) M (IHC, WB) H CD38 H M H (FC, IHC, IP, WB) M (FC, WB) GLI-2 H (ChIP, IHC, WB) M (IHC, WB) H CD138/Syndecan-1 H M H (ELISA, FC, IHC, WB) M (FC, IHC, IP, WB) H MICL/CLEC12A H (FC, IHC, WB) M (FC, IHC, WB) Osteosarcoma Cancer Stem Cell Markers Musashi-2 H (IHC, WB) ABCG2 H (FC, IHC) TIM-3 H M H (FC, WB) M (FC, WB) H Nestin H (FC, IHC) M (FC, IHC, WB) R (FC, IHC, WB) Liver Cancer Stem Cell Markers STRO-1 H (FC, IHC) α-Fetoprotein/AFP H (FC, IHC, WB) M (FC, IHC, WB) H Ovarian Cancer Stem Cell Markers Aminopeptidase N/ H M H (FC, IHC, IP, WB) M (FC, IHC, IP, WB) CD44 H M R P H (FC, IHC, IP, WB) M (B/N, FC, IHC, WB) H ANPEP R (B/N, FC, IHC, WB) Ca (FC) CD90/Thy1 H (FC, WB) M (WB) CD117/SCF R/c-kit H H (B/N, ELISA, FC, IHC, WB) M (FC, IHC, WB) H NF2/Merlin H (IHC, WB) Pancreatic Cancer Stem Cell Markers Lung Cancer Stem Cell Markers BMI-1 H (ChIP, FC, IHC, WB) H ABCG2 H (FC, IHC) CD24 H H (FC, IHC, WB) H Aldehyde H H (IHC, IP, WB) CD44 H M R P H (FC, IHC, IP, WB) M (B/N, FC, IHC, WB) H Dehydrogenase 1-A1/ R (B/N, FC, IHC, WB) Ca (FC) ALDH1A1 CXCR4 H (B/N, FC, IHC) M (B/N, FC, IHC) F (FC, IHC) H CD90/Thy1 H (FC, WB) M (WB) EpCAM/TROP1 H H (ELISA, FC, IHC, WB) H H CD117/SCF R/c-kit H H (B/N, ELISA, FC, IHC, WB) M (FC, IHC, WB) H Prostate Cancer Stem Cell Markers EpCAM/TROP1 H H (ELISA, FC, IHC, WB) H H ABCG2 H (FC, IHC) Melanoma Cancer Stem Cell Markers BMI-1 H (ChIP, FC, IHC, WB) H ABCB5 H (WB) CD44 H M R P H (FC, IHC, IP, WB) M (B/N, FC, IHC, WB) H ABCG2 H (FC, IHC) R (B/N, FC, IHC, WB) Ca (FC) CD20/MS4A1 H (FC) c-Myc H (ChIP, IHC, WB) H CD166/ALCAM H M H (B/N, ELISA, FC, WB) M (FC, IHC, WB) H M Integrin α2b1 H Species Key: H Human M Mouse R Rat B Bovine Ca Canine CR Cotton Rat F Feline P Porcine Application Key: B/N Blocking/Neutralization ChIP Chromatin Immunoprecipitation ELISA ELISA Capture and/or Detection FC Flow Cytometry IHC Immunohistochemistry IP Immunoprecipitation WB Western blot STRO-1 in the Human MG-63 Cell Line.