Localization of CD44 and CD90 positive cells to the invasive front of breast tumors
Open accessAbstract
Background: A variety of markers have been proposed to identify breast cancer stem cells. Here, we used immunohistostaining and flow cytometry to analyze their interrelationships and to sort cells for tumorigenicity studies. Methods: Cytokeratin, CD44, and CD90 were localized to primary breast cancer and normal breast (NB) tissue by immunohistostaining and related to CD117 and CD133 expression by flow cytometry. Immunodeficient NOD.CB17‐Prkdc scid/J and NOD.Cg‐Prkdc scid Il2rg tm1Wjl/SzJ mice were used to test tumorigenicity of sorted CD90+ low‐light scatter, CD90+ high‐light scatter, and CD90 neg tumor cells. Results: NB basal cells coexpressed CD44 and CD90. As cells transited luminally, CD44 was retained and downmodulated, and CD90 was lost and cytokeratin increased. In breast tumors, basal‐like CD44+/CD90+ cells were localized to the tumor periphery, adjacent to CD90+ stroma. Like normal luminal cells, interior tumor cells were CD44+/CD90−. Immunophenotyping (CD44/CD90/CD117/CD133) of cytokeratin+ cells revealed no significant difference in expression between tumors and tumor‐free breast. In both, CD133 was distributed approximately equally among CD44/CD90 subsets, whereas CD117 expression was highest in the basal‐associated CD44+/CD90+ subset. Sorted CD90+ pleural effusion cells with lymphoid light scatter, 49% of which were CD44+, were uniquely tumorigenic in immunodeficient mice (100 cells/injection). Conclusions: Our data demonstrate that all tumors contain a small population of CD44+/CD90+ cells, mimicking the phenotype of ductal‐basal cells. These are localized to the tumor periphery, adjacent to CD90+ stroma. Among the nonhematopoietic, nonmesothelial cells found in metastatic pleural effusions, low‐light scatter CD90+ cells are most potently tumorigenic, compared to high‐scatter CD90+ cells and CD90− cells. © 2010 International Clinical Cytometry Society
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
Small resting CD90+ breast cancer cells form tumors with high efficiency, requiring fewer than 100 cells per injection, and do so independently of supportive stroma or adipose-derived stem/stromal cells.
“Small (low light scatter) resting CD90+ breast cancer cells give rise to tumors with high efficiency (<100 cells/injection) [90, 99], independently of supportive stroma/ASC [51].”
From Mesenchymal stem cell secretome and regenerative therapy after cancer (2013) · cites this paper as [90]
The Discussion (‘Size Matters’; page unavailable) reports tumor formation from ≤60 CD44+/CD90+ low-light-scatter cells in a previous study. This paper’s own experiments used 100 sorted cells per site and found tumors at 5%–25% of sites. Neither experiment establishes independence from supportive cells: the Discussion says all injected populations received irradiated tumor cells and Matrigel, potentially providing a niche effect. (LLM, conf=0.88)
Experimental — accuracy not yet measured
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 59 · Cited by 62
- Authors
- Donnenberg, V. S., Donnenberg, A. D., Zimmerlin, L., Landreneau, R. J., Bhargava, R., Wetzel, R. A., Basse, P., & Brufsky, A. M.
- Affiliations
- University of Pittsburgh (US)
- Corresponding author
- Donnenberg, Vera S.
- ORCID
- Venue
- Cytometry Part B: Clinical Cytometry
- Publisher
- Wiley
- Published
- 2010-04-30
- Volume
- 78B
- Issue
- 5
- Pages
- 287-301
- ISSN
- 1552-4949 (ISSN-L)
- 1552-4957
- PMC
- PMC4165077
- OpenAlex
- W1990813262
- Cited by
- 62
- References
- 59
- Citations by year
- 2025: 1 · 2023: 3 · 2022: 4 · 2021: 1 · 2020: 1 · 2019: 2 · 2018: 7 · 2017: 5 · 2016: 5 · 2015: 5 · 2014: 6 · 2013: 5 · 2012: 11
- FWCI
- 3.47
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Cytometry Part B Clinical Cytometry (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- Cancer Institute, University of Pittsburgh
- National Cancer Institute (P30CA047904)
- Topics
- Health Sciences › Medicine › Oncology › Cancer Cells and Metastasis
- Health Sciences › Medicine › Genetics › Mesenchymal stem cell research
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Developmental Biology and Gene Regulation
- Keywords
- CD44, CD90, CD117, CD133, tumor periphery, pleural effusion, tumorigenicity, tumor stroma, cytokeratin, light scattering, immunodeficient mice
- MeSH terms
- AC133 Antigen, Adenocarcinoma, Animals, Breast Neoplasms, Female, Flow Cytometry, Glycoproteins, Humans, Keratins, Neoplasm Invasiveness, Peptides, Biomarkers, Tumor, Neoplastic Stem Cells, Antigens, CD, Pleural Effusion, Malignant, Mice, Inbred NOD, Thy-1 Antigens, Hyaluronan Receptors, Proto-Oncogene Proteins c-kit, Xenograft Model Antitumor Assays, Mice
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
