Molecular characterization of CD44+/CD24−/Ck+/CD45− cells in benign and malignant breast lesions

Paula, Arnaud Da Cruz; Leitão, Catarina; Marques, Oriana; Rosa, Ana; Santos, Ana Filipa L.O.M.; Rêma, Alexandra; Faria, Maria De Fátima; Rocha, Ana Mafalda; Costa, José Luís; Lima, Margarida; Lopes, Carlos

doi:10.1007/s00428-017-2068-4

Cited by 14 publications

(4 citation statements)

References 44 publications

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“…Additionally, CD44 expression was an independent prognostic factor in multivariate analysis. Similar to our results, previous studies showed that the overexpression of CD44 is evidence of worse clinical behavior and shorter progression-free survival [20,23,13,24].…”

Section: Discussionsupporting

confidence: 92%

TP53 Mutation in Saudi Breast Cancer Patients: Correlations with Cancer Stem Cell Markers Expression and Clinicopathological Variables

Nassir¹,

Elmoneim²,

Esheba³

et al. 2020

SJPM

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Background: Breast cancer is one of the most common cancers with a high mortality rate worldwide including Saudi Arabia. It is characterized by the presence of both intra-and inter-tumor heterogeneity. It describes the origin of this heterogeneity to the cancer stem cells (CSC). Breast cancer stem cells are characterized by the expression of the surface markers CD44 and lack or very low expression of CD24. Objectives: To assess cancer stem cell markers (CD44 andCD24) in 126 breast cancer cases by immunohistochemistry and study their association with a different type of TP53 gene mutations by applying next-generation sequencing (NGS). In addition to analyze the association between these markers and the clinicopathological characteristics. Results: CD44 expression was significantly associated with lymph node metastasis, tumor grade, stage (each P<0.0001), and ER expression (P = 0.016). CD24 expression was found to be associated with lymph node metastasis and ER only. For the molecular analysis, the number of mutations per case was significantly associated with the advanced stage of breast cancer (p = 0.004). Also, missense mutation was highly associated with CD44 and CD24 (p=0.04, p=0.005), respectively. Stop-gained mutation and Frameshift mutation both were associated with CD44 only (p=0.01, p=0.05), respectively. Finally, the synonymous mutation was only associated with the stage of cancer (p=0.01). Conclusion, we believe that the combination of CD44, CD24, TP53 and TP53 gene mutations can be prognostic factors for breast cancer patients and the information obtained may contribute to the development of a treatment.

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Section: Discussionsupporting

confidence: 92%

TP53 Mutation in Saudi Breast Cancer Patients: Correlations with Cancer Stem Cell Markers Expression and Clinicopathological Variables

Nassir¹,

Elmoneim²,

Esheba³

et al. 2020

SJPM

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“…In other studies, CD44 high /CD133 high cells showed increased tumorigenic capabilities ( 334 ). Also in breast cancers, the percentage of CD44 + /CD24 − / CK + /CD45 − cells was shown to be increased in malignant lesions compared to non-malignant lesions ( 139 ). A significant decrease in proliferation and migration of breast cancer cells was observed after the knock-down of CD44 ( 140 ).…”

Section: Cscs and Their Origin At Tumor Initiationmentioning

confidence: 99%

Cancer Stem Cells—Origins and Biomarkers: Perspectives for Targeted Personalized Therapies

et al. 2020

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The use of biomarkers in diagnosis, therapy and prognosis has gained increasing interest over the last decades. In particular, the analysis of biomarkers in cancer patients within the pre- and post-therapeutic period is required to identify several types of cells, which carry a risk for a disease progression and subsequent post-therapeutic relapse. Cancer stem cells (CSCs) are a subpopulation of tumor cells that can drive tumor initiation and can cause relapses. At the time point of tumor initiation, CSCs originate from either differentiated cells or adult tissue resident stem cells. Due to their importance, several biomarkers that characterize CSCs have been identified and correlated to diagnosis, therapy and prognosis. However, CSCs have been shown to display a high plasticity, which changes their phenotypic and functional appearance. Such changes are induced by chemo- and radiotherapeutics as well as senescent tumor cells, which cause alterations in the tumor microenvironment. Induction of senescence causes tumor shrinkage by modulating an anti-tumorigenic environment in which tumor cells undergo growth arrest and immune cells are attracted. Besides these positive effects after therapy, senescence can also have negative effects displayed post-therapeutically. These unfavorable effects can directly promote cancer stemness by increasing CSC plasticity phenotypes, by activating stemness pathways in non-CSCs, as well as by promoting senescence escape and subsequent activation of stemness pathways. At the end, all these effects can lead to tumor relapse and metastasis. This review provides an overview of the most frequently used CSC markers and their implementation as biomarkers by focussing on deadliest solid (lung, stomach, liver, breast and colorectal cancers) and hematological (acute myeloid leukemia, chronic myeloid leukemia) cancers. Furthermore, it gives examples on how the CSC markers might be influenced by therapeutics, such as chemo- and radiotherapy, and the tumor microenvironment. It points out, that it is crucial to identify and monitor residual CSCs, senescent tumor cells, and the pro-tumorigenic senescence-associated secretory phenotype in a therapy follow-up using specific biomarkers. As a future perspective, a targeted immune-mediated strategy using chimeric antigen receptor based approaches for the removal of remaining chemotherapy-resistant cells as well as CSCs in a personalized therapeutic approach are discussed.

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“…9 Using flow cytometry, the same group found the frequency of CD44+/CD24−/CK+/CD45− cells in DCIS ranges from 2.6–18%. 10 However, Ki67 low , AKT1 low QCCs do not clearly express the marker profile ascribed to cancer ‘stem cells’ e.g., CD44 high /CD24 low 4 . This suggests that there are likely multiple populations of quiescent cancer cells in DCIS but the morphologic and functional overlap between them remains to be elucidated.…”

Section: Discussionmentioning

confidence: 99%

AKT1low quiescent cancer cells in ductal carcinoma in situ of the breast

et al. 2019

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Ductal carcinoma in situ (DCIS) of the breast precedes the development of invasive breast cancer and reflects the genomic changes and protein expression profile of invasive disease. AKT1low cancer cells (QCC) are a rare, drug-tolerant, epigenetically plastic, and quiescent cancer cell subset that we previously identified at a frequency of 0.5–1% in primary breast tumors using the marker profile: AKTlow/H3K9me2low/HES1high. Here we used quantitative immunofluorescence microscopy with computational image analysis to show that AKT1low QCCs are present in DCIS from patients with and without co-existing invasive breast cancer. These data suggest that a drug-resistant, quiescent cancer cell state is present in premalignant breast lesions prior to the development of invasive disease. These findings warrant further study of whether AKT1low QCCs contribute to invasive tumor development and recurrence, similar to their role in more advanced malignancy.

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Molecular characterization of CD44+/CD24−/Ck+/CD45− cells in benign and malignant breast lesions

Cited by 14 publications

References 44 publications

TP53 Mutation in Saudi Breast Cancer Patients: Correlations with Cancer Stem Cell Markers Expression and Clinicopathological Variables

TP53 Mutation in Saudi Breast Cancer Patients: Correlations with Cancer Stem Cell Markers Expression and Clinicopathological Variables

Cancer Stem Cells—Origins and Biomarkers: Perspectives for Targeted Personalized Therapies

AKT1low quiescent cancer cells in ductal carcinoma in situ of the breast

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