Cancer stem cell subpopulations within the CD44high human breast cancer stem cell compartment
Ontology highlight
ABSTRACT:
ORGANISM(S): Homo sapiens
SUBMITTER: Leth-Larsen Rikke
PROVIDER: S-ECPF-GEOD-32455 | biostudies-other |
REPOSITORIES: biostudies-other
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Project description:The CD44hi compartment in human breast cancer is enriched in tumor-initiating cells, however the functional heterogeneity within this subpopulation remains poorly defined. From a human breast cancer cell line with a known bi-lineage phenotype we have isolated and cloned two CD44hi populations that exhibited mesenchymal/Basal B and luminal/Basal A features, respectively. Rather than CD44+/CD24-,Basal B (G4) cells, only CD44hi/CD24lo, epithelioid Basal A (A4) cells retained a tumor-initiating capacity in NOG mice, form mammospheres and exhibit resistance to standard chemotherapy. Microarray data obtained from Affymetrix Human Gene 1.0 ST Array Five replicates of A4 and 5 replicates of G4
2012-06-11 | E-GEOD-32455 | biostudies-arrayexpress
Project description:The CD44hi compartment in human breast cancer is enriched in tumor-initiating cells, however the functional heterogeneity within this subpopulation remains poorly defined. From a human breast cancer cell line with a known bi-lineage phenotype we have isolated and cloned two CD44hi populations that exhibited mesenchymal/Basal B and luminal/Basal A features, respectively. Rather than CD44+/CD24-,Basal B (G4) cells, only CD44hi/CD24lo, epithelioid Basal A (A4) cells retained a tumor-initiating capacity in NOG mice, form mammospheres and exhibit resistance to standard chemotherapy. Microarray data obtained from Affymetrix Human Gene 1.0 ST Array
2012-06-12 | GSE32455 | GEO
Project description:The CD44hi compartment in human breast cancer is enriched in tumor-initiating cells, however the functional heterogeneity within this subpopulation remains poorly defined. From a human breast cancer cell line with a known bi-lineage phenotype we have isolated and cloned CD44hi populations that exhibited mesenchymal/Basal B and luminal/Basal A features, respectively:CD44+/CD24-,Basal B (G4, H6) cells and CD44hi/CD24lo epithelioid Basal A (A4, AB) cells. Seven replicates of A4, seven replicates of G4, three replicates of AB, three replicates of H6
2015-04-30 | E-GEOD-59281 | biostudies-arrayexpress
Project description:The CD44hi compartment in human breast cancer is enriched in tumor-initiating cells, however the functional heterogeneity within this subpopulation remains poorly defined. From a human breast cancer cell line with a known bi-lineage phenotype we have isolated and cloned CD44hi populations that exhibited mesenchymal/Basal B and luminal/Basal A features, respectively:CD44+/CD24-,Basal B (G4, H6) cells and CD44hi/CD24lo epithelioid Basal A (A4, AB) cells.
2015-04-30 | GSE59281 | GEO
Project description:The CD44(hi) compartment in human breast cancer is enriched in tumor-initiating cells; however, the functional heterogeneity within this subpopulation remains poorly defined. We used a triple-negative breast cancer cell line with a known bilineage phenotype to isolate and clone CD44(hi) single cells that exhibited mesenchymal/basal B and luminal/basal A features, respectively. Herein, we demonstrate in this and other triple-negative breast cancer cell lines that, rather than CD44(hi)/CD24(-) mesenchymal-like basal B cells, the CD44(hi)/CD24(lo) epithelioid basal A cells retained classic cancer stem cell features, such as tumor-initiating capacity in vivo, mammosphere formation and resistance to standard chemotherapy. These results complement previous findings using oncogene-transformed normal mammary cells showing that only cell clones with a mesenchymal phenotype exhibit cancer stem cell features. Further, we performed comparative quantitative proteomic and gene array analyses of these cells and identified potential novel markers of breast cancer cells with tumor-initiating features, such as lipolysis-stimulated lipoprotein receptor (LSR), RAB25, S100A14 and mucin 1 (MUC1), as well as a novel 31-gene signature capable of predicting distant metastasis in cohorts of estrogen receptor-negative human breast cancers. These findings strongly favor functional heterogeneity in the breast cancer cell compartment and hold promise for further refinements of prognostic marker profiling. Our work confirms that, in addition to cancer stem cells with mesenchymal-like morphology, those tumor-initiating cells with epithelial-like morphology should also be the focus of drug development.
| S-EPMC3474436 | biostudies-literature
Project description:Heterogeneity is a feature of stem cell populations, resulting from innate cellular hierarchies that govern differentiation capability. How heterogeneity impacts human pluripotent stem cell populations is directly relevant to their efficacious use in regenerative medicine applications. The control of pluripotency is asserted by a core transcription factor network, of which Oct4 is a necessary member. In mouse embryonic stem cells (ESCs), the zinc finger transcription factor Rex1 (Zfp42) closely tracks the undifferentiated state and is capable of segregating Oct4 positive mESCs into metastable populations expressing or lacking Rex1 that are inter-convertible. However, little is currently understood about the extent or function of heterogeneous populations in the human pluripotent compartment. Human ESCs express REX1 transcripts but the distribution and properties of REX1 expressing cells have yet to be described. To address these questions, we used gene targeting in human ESCs to insert the fluorescent protein Venus and an antibiotic selection marker under the control of the endogenous REX1 transcription regulatory elements, generating a sensitive, selectable reporter of pluripotency. REX1 is co-expressed in OCT4 and TRA-1-60 positive hESCs and rapidly lost upon differentiation. Importantly, REX1 expression reveals significant heterogeneity within seemingly homogenous populations of OCT4 and TRA-1-60 hESCs. REX1 expression is extinguished before OCT4 during differentiation, but, in contrast to the mouse, loss of REX1 expression demarcates a stable, OCT4 positive lineage-primed state in pluripotent hESCs that does not revert back to REX1 positivity under normal conditions. We show that loss of REX1 expression correlates with altered patterns of DNA methylation at the REX1 locus, implying that epigenetic mechanisms may interfere with the metastable phenotype commonly found in murine pluripotency.
| S-EPMC3578859 | biostudies-literature
Project description:AimTo identify and characterize cancer stem cells (CSCs) in moderately differentiated lip squamous cell carcinoma (MDLSCC).MethodMDLSCC samples underwent 3,3-diaminobenzidine (DAB) immunohistochemical (IHC) staining for squamous cell carcinoma marker EMA, CSC marker CD44 and embryonic stem cell markers NANOG, octamer-binding transcription factor 4 (OCT4), spalt-like transcription factor 4 (SALL4), sex-determining region Y-box 2 (SOX2), and phosphorylated signal transducer and activator of transcription 3 (pSTAT3). Immunofluorescent IHC staining was performed on two MDLSCC samples. Western blotting (WB) was used to confirm the expression of the aforementioned proteins and their transcription activation was investigated using NanoString and RT-qPCR.ResultsIHC staining demonstrated the presence of (1) an EMA+/CD44+/SALL4+/NANOG+/pSTAT3+/SOX2+/OCT4- CSC subpopulation within the tumor nests (TNs); (2) a CD44+/SALL4+/NANOG+/pSTAT3+/SOX2+/OCT4- CSC subpopulation; and (3) a CD44+/SALL4+/NANOG+/pSTAT3+/SOX2+/OCT4+ CSC subpopulation within the stroma, between the TNs. NanoString and RT-qPCR confirmed the presence of mRNA for CD44, SALL4, STAT3, SOX2, and OCT4, and WB confirmed the presence of NANOG, pSTAT3, SOX2, and OCT4.ConclusionThis study demonstrates three putative CSC subpopulations within MDLSCC.
| S-EPMC5337496 | biostudies-literature
Project description:Cancer stem cells (CSCs) have been identified in many cancer types including primary head and neck cutaneous squamous cell carcinoma (HNcSCC). This study aimed to identify and characterize CSCs in metastatic HNcSCC (mHNcSCC). Immunohistochemical staining performed on mHNcSCC samples from 15 patients demonstrated expression of the induced pluripotent stem cell (iPSC) markers OCT4, SOX2, NANOG, KLF4, and c-MYC in all 15 samples. In situ hybridization and RT-qPCR performed on four of these mHNcSCC tissue samples confirmed transcript expression of all five iPSC markers. Immunofluorescence staining performed on three of these mHNcSCC samples demonstrated expression of c-MYC on cells within the tumor nests (TNs) and the peri-tumoral stroma (PTS) that also expressed KLF4. OCT4 was expressed on the SOX2+/NANOG+/KLF4+ cells within the TNs, and the SOX2+/NANOG+/KLF4+ cells within the PTS. RT-qPCR demonstrated transcript expression of all five iPSC markers in all three mHNcSCC-derived primary cell lines, except for SOX2 in one cell line. Western blotting showed the presence of SOX2, KLF4, and c-MYC but not OCT4 and NANOG in the three mHNcSCC-derived primary cell lines. All three cell lines formed tumorspheres, at the first passage. We demonstrated an OCT4+/NANOG+/SOX2+/KLF4+/c-MYC+ CSC subpopulation and an OCT4+/NANOG-/SOX2+/KLF4+/c-MYC+ subpopulation within the TNs, and an OCT4+/NANOG+/SOX2+/KLF4+/c-MYC+ subpopulation within the PTS of mHNcSCC.
| S-EPMC7406827 | biostudies-literature
Project description:BackgroundCancer stem cells (CSCs) are regarded as the cause of tumor formation and recurrence. The isolation and identification of CSCs could help to develop novel therapeutic strategies specifically targeting CSCs.MethodsHuman hepatoma cell lines were plated in stem cell conditioned culture system allowed for sphere forming. To evaluate the stemness characteristics of spheres, the self-renewal, proliferation, chemoresistance, tumorigenicity of the PLC/PRF/5 sphere-forming cells, and the expression levels of stem cell related proteins in the PLC/PRF/5 sphere-forming cells were assessed, comparing with the parental cells. The stem cell RT-PCR array was performed to further explore the biological properties of liver CSCs.ResultsThe PLC/PRF/5, MHCC97H and HepG2 cells could form clonal nonadherent 3-D spheres and be serially passaged. The PLC/PRF/5 sphere-forming cells possessed a key criteria that define CSCs: persistent self-renewal, extensive proliferation, drug resistance, overexpression of liver CSCs related proteins (Oct3/4, OV6, EpCAM, CD133 and CD44). Even 500 sphere-forming cells were able to form tumors in NOD/SCID mice, and the tumor initiating capability was not decreased when spheres were passaged. Besides, downstream proteins DTX1 and Ep300 of the CSL (CBF1 in humans, Suppressor of hairless in Drosophila and LAG1 in C. elegans) -independent Notch signaling pathway were highly expressed in the spheres, and a gamma-secretase inhibitor MRK003 could significantly inhibit the sphere formation ability.ConclusionsNonadherent tumor spheres from hepatoma cell lines cultured in stem cell conditioned medium possess liver CSC properties, and the CSL-independent Notch signaling pathway may play a role in liver CSCs.
| S-EPMC3136412 | biostudies-literature
Project description:CAPNS1 is essential for the stability and function of ubiquitous CAPN1 and CAPN2. Calpain modulates by proteolytic cleavage many cellular substrates and its activity is often deregulated in cancer cells, therefore calpain inhibition has been proposed as a therapeutical strategy for a number of malignancies. Here we show that CAPNS1 depletion is coupled to impairment of MCF7 and MCF10AT cell lines growth on plate and defective architecture of mammary acini derived from MCF10A cells. In soft agar CAPNS1 depletion leads to cell growth increase in MCF7, and decrease in MCF10AT cells. In both MCF7 and MCF10AT, CAPNS1 depletion leads to the enlargement of the stem cell compartment, as demonstrated by mammosphere formation assays and evaluation of stem cell markers by means of FACS and western blot analysis. Accordingly, activation of calpain by thapsigargin treatment leads to a decrease in the stem cell reservoir. The expansion of the cancer stem cell population in CAPNS1 depleted cells is coupled to a defective shift from symmetric to asymmetric division during mammosphere growth coupled to a decrease in NUMB protein level.
| S-EPMC4825769 | biostudies-literature