Correlation of Breast Cancer Axillary Lymph Node Metastases With Stem Cell Mutations

Donovan, Cory; Pommier, Rodney F.; Schillace, Robynn V.; O'Neill, Steven; Müller, Patrick; Alabran, Jennifer L.; Hansen, Juliana E.; Murphy, John C.; Naik, Arpana; Vetto, John T.; Pommier, SuEllen J.

doi:10.1001/jamasurg.2013.3028

Cited by 17 publications

(13 citation statements)

References 34 publications

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“…The CSC theory was proposed to explain the heterogeneity in the biology of cancer cells (Marusyk and Polyak 2010). CSCs are supposed to have metastatic potential and natural resistance to the chemotherapy and radiotherapy (Donovan et al 2013;Sterlacci et al 2014). EMT is a process wherein epithelial cells gradually transform into mesenchymal-like cells and could also be one of the causes of morphological tumor heterogeneity (Bartis et al 2013).…”

Section: Introductionmentioning

confidence: 99%

Comparison of the expression levels of molecular markers among the peripheral area and central area of primary tumor and metastatic lymph node tumor in patients with squamous cell carcinoma of the lung

Udagawa

Ishii

Morise

et al. 2015

J Cancer Res Clin Oncol

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Section: Introductionmentioning

confidence: 99%

Comparison of the expression levels of molecular markers among the peripheral area and central area of primary tumor and metastatic lymph node tumor in patients with squamous cell carcinoma of the lung

Udagawa

Ishii

Morise

et al. 2015

J Cancer Res Clin Oncol

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“…In addition, the data presented here indicate that the gene and protein expression of BCSCs may vary from that of other cells within a tumor. Because BCSCs are a rare population of cells within a tumor, they are not accurately tested by random sampling of whole tumor specimens [ 48 ]. Thus, from a clinical perspective, determining the gene and protein status of directly isolated BCSCs from each patient tumor may prove to be critical for informed care management.…”

Section: Discussionmentioning

confidence: 99%

Estrogen receptor, progesterone receptor, interleukin-6 and interleukin-8 are variable in breast cancer and benign stem/progenitor cell populations

et al. 2014

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BackgroundEstrogen receptor positive breast cancers have high recurrence rates despite tamoxifen therapy. Breast cancer stem/progenitor cells (BCSCs) initiate tumors, but expression of estrogen (ER) or progesterone receptors (PR) and response to tamoxifen is unknown. Interleukin-6 (IL-6) and interleukin-8 (IL-8) may influence tumor response to therapy but expression in BCSCs is also unknown.MethodsBCSCs were isolated from breast cancer and benign surgical specimens based on CD49f/CD24 markers. CD44 was measured. Gene and protein expression of ER alpha, ER beta, PR, IL-6 and IL-8 were measured by proximity ligation assay and qRT-PCR.ResultsGene expression was highly variable between patients. On average, BCSCs expressed 10-106 fold less ERα mRNA and 10-103 fold more ERβ than tumors or benign stem/progenitor cells (SC). BCSC lin-CD49f−CD24−cells were the exception and expressed higher ERα mRNA. PR mRNA in BCSCs averaged 10-104 fold less than in tumors or benign tissue, but was similar to benign SCs. ERα and PR protein detection in BCSCs was lower than ER positive and similar to ER negative tumors. IL-8 mRNA was 10-104 higher than tumor and 102 fold higher than benign tissue. IL-6 mRNA levels were equivalent to benign and only higher than tumor in lin-CD49f−CD24−cells. IL-6 and IL-8 proteins showed overlapping levels of expressions among various tissues and cell populations.ConclusionsBCSCs and SCs demonstrate patient-specific variability of gene/protein expression. BCSC gene/protein expression may vary from that of other tumor cells, suggesting a mechanism by which hormone refractory disease may occur.Electronic supplementary materialThe online version of this article (doi:10.1186/1471-2407-14-733) contains supplementary material, which is available to authorized users.

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“…Indeed, when depleted in HSCs, NSCs or prostate stem cells, PTEN can lead to leukaemia [ 123 ], brain or prostate tumorigenesis, respectively [ 121 ]. Mutations in PI3K and AKT were reported in breast CSCs, but also in other cancers, and might be related with tumour proliferation [ 124 ].…”

Section: Age-associated Genetic Events and Generation Of Cscsmentioning

confidence: 99%

The crossroads between cancer stem cells and aging

et al. 2015

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The cancer stem cell (CSC) hypothesis suggests that only a subpopulation of cells within a tumour is responsible for the initiation and progression of neoplasia. The original and best evidence for the existence of CSCs came from advances in the field of haematological malignancies. Thus far, putative CSCs have been isolated from various solid and non-solid tumours and shown to possess self-renewal, differentiation, and cancer regeneration properties. Although research in the field is progressing extremely fast, proof of concept for the CSC hypothesis is still lacking and key questions remain unanswered, e.g. the cell of origin for these cells. Nevertheless, it is undisputed that neoplastic transformation is associated with genetic and epigenetic alterations of normal cells, and a better understanding of these complex processes is of utmost importance for developing new anti-cancer therapies. In the present review, we discuss the CSC hypothesis with special emphasis on age-associated alterations that govern carcinogenesis, at least in some types of tumours. We present evidence from the scientific literature for age-related genetic and epigenetic alterations leading to cancer and discuss the main challenges in the field.

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Correlation of Breast Cancer Axillary Lymph Node Metastases With Stem Cell Mutations

Cited by 17 publications

References 34 publications

Comparison of the expression levels of molecular markers among the peripheral area and central area of primary tumor and metastatic lymph node tumor in patients with squamous cell carcinoma of the lung

Comparison of the expression levels of molecular markers among the peripheral area and central area of primary tumor and metastatic lymph node tumor in patients with squamous cell carcinoma of the lung

Estrogen receptor, progesterone receptor, interleukin-6 and interleukin-8 are variable in breast cancer and benign stem/progenitor cell populations

The crossroads between cancer stem cells and aging

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