Cell-in-Cell Structure Mediates In-Cell Killing Suppressed by CD44
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ABSTRACT:
PROVIDER: PRJNA733823 | ENA |
REPOSITORIES: ENA
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Project description:Penetration of immune cells into tumor cells was believed to be immune-suppressive via cell-in-cell (CIC) mediated death of the internalized immune cells. We unexpectedly found that CIC formation largely led to the death of the host tumor cells, but not the internalized immune cells, manifesting typical features of death executed by NK cells, which we called “in-cell killing” that demonstrates efficacy superior to the canonical way of “kiss killing” from outside. By expression profiling of isogenic cells, CD44 on tumor cells was identified as a negative regulator of “in-cell killing” via inhibiting CIC formation. CD44 functions to antagonize NK cell internalization by reducing N-cadherin-mediated intercellular adhesion and enhancing Rho GTPase-regulated cellular stiffness as well. Remarkably, antibody-mediated blockade of CD44 signaling potentiated the suppressive effects of NK cells on tumor growth associated with increased heterotypic CIC formation. Together, we identified CIC-mediated “in-cell killing” as a promising strategy for cancer immunotherapy.
2024-05-20 | GSE175819 | GEO
Project description:Penetration of immune cells into tumor cells was believed to be immune-suppressive via cell-in-cell (CIC) mediated death of the internalized immune cells. We unexpectedly found that CIC formation largely led to the death of the host tumor cells, but not the internalized immune cells, manifesting typical features of death executed by NK cells; we named this "in-cell killing" which displays the efficacy superior to the canonical way of "kiss-killing" from outside. By profiling isogenic cells, CD44 on tumor cells was identified as a negative regulator of "in-cell killing" via inhibiting CIC formation. CD44 functions to antagonize NK cell internalization by reducing N-cadherin-mediated intercellular adhesion and by enhancing Rho GTPase-regulated cellular stiffness as well. Remarkably, antibody-mediated blockade of CD44 signaling potentiated the suppressive effects of NK cells on tumor growth associated with increased heterotypic CIC formation. Together, we identified CIC-mediated "in-cell killing" as a promising strategy for cancer immunotherapy.
| S-EPMC9016064 | biostudies-literature
Project description:To understand the role of p53 in regulating stem cell population (CD24-CD44+) and stemness-associated miRNAs, we first compared miRNA expression profiles between human mammary epithelical cells knocked-down p53 and control cells. We then cross-referenced p53-regulated miRNAs with stemness-associated miRNAs analyzed from expression profiling of sorted CD24-CD44+ and non-CD24-CD44+ cell populations. Further biological experiments were performed with the miRNAs that are altered in CD24-CD44+ stem cell populations and also regulated by p53. Total RNAs, including miRNAs, extracted from CD24-CD44+ cells (labeled in Hy3) and non-CD24-CD44+ cells (labeled in Hy5) were hybridized on Exiqon miRCURY LNA arrays according to the manufacturer's protocol.
2011-02-01 | E-GEOD-25036 | biostudies-arrayexpress
Project description:To understand the role of p53 in regulating stem cell population (CD24-CD44+) and stemness-associated miRNAs, we first compared miRNA expression profiles between human mammary epithelical cells knocked-down p53 and control cells. We then cross-referenced p53-regulated miRNAs with stemness-associated miRNAs analyzed from expression profiling of sorted CD24-CD44+ and non-CD24-CD44+ cell populations. Further biological experiments were performed with the miRNAs that are altered in CD24-CD44+ stem cell populations and also regulated by p53.
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Project description:CD44 is a transmembrane glycoprotein playing a key role in cel adhesion to the extracellular matrix. CD44 expression is upregulated in various cancer cells and recognized as a molecular marker for tumor-initiating cancer cells. However, the intricate correlation between CD44 and underlying biological functions is yet to be fully disclosed at molecular levels. Here, we discovererd global proteome changes induced by CD44 knockdown in the four different breast cancer cell lines by TMT based quantitative proteomics.
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Project description:To identify genes that are differentially expressed between CD44+ and CD44- cells in colonospheres, we have employed whole genome microarray expression profiling as a discovery platform. Colonospheres from four colon cancer patients were sorted into CD44+ and CD44- cells using the FACS Aria II Cell Sorter, and total RNA extracted from the cells were labeled with Cy3 and used for microarray analyses with Agilent Whole Human Genome Oligo Microarrays. Gene expression in fluorescence-activated cell-sorted CD44+ and CD44- cells derived from four colon cancer patients was measured.
2012-12-07 | E-GEOD-38706 | biostudies-arrayexpress
Project description:To identify genes that are differentially expressed between CD44+ and CD44- cells in colonospheres, we have employed whole genome microarray expression profiling as a discovery platform. Colonospheres from four colon cancer patients were sorted into CD44+ and CD44- cells using the FACS Aria II Cell Sorter, and total RNA extracted from the cells were labeled with Cy3 and used for microarray analyses with Agilent Whole Human Genome Oligo Microarrays.
2012-12-07 | GSE38706 | GEO
Project description:CD44+/CD24- subpopulation of normal and cancerous breast epithelial cells are suggested to have stem cell properties. The goal of this study was to identify gene expression differences between CD44+/CD24- and CD44-/CD24+ subpopulation of cells from a same cell lines. We selected MCF-10A cells, which are immortalized derived from a fibrocystic breast disease. These cells are immortalized but not transformed and express basal cell markers. Cells were from a single sort but plated into four 100 mm plates. RNA was prepared from each plate separately for the analysis. Comparison of gene expression between 2 groups ( CD44+/CD24- and CD44-/CD24+) 4 replicates each.
2010-03-07 | E-GEOD-15192 | biostudies-arrayexpress
Project description:We hypothesized that CD44+ tumor cells might have an increased capacity for reactive oxygen species (ROS) defense in the gastric tumors of K19-Wnt1/C2mE mice. To address this possibility, we examined the expression of antioxidant genes in tumor cells isolated from K19-Wnt1/C2mE mice by fluorescence-activated cell sorting (FACS). Lineage marker (Lin)–negative cells that were CD44+ or CD44– were thus isolated from the gastric tumors of 30-week-old K19-Wnt1/C2mE mice and subjected to cDNA microarray analysis. The expression of several key antioxidant genes, including those for glutathione peroxidase (GPX) and peroxiredoxin (PRDX) isoforms, was found to be increased in CD44+ tumor cells compared with that in CD44– cells.
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