Gene Expression Signatures in Circulating Tumor Cells Correlate with Response to Therapy in Metastatic Breast Cancer

Bredemeier, Maren; Edimiris, Philippos; Mach, Paweł; Kubista, Mikael; Sjöback, Robert; Rohlova, Eva; Kološtová, Katarína; Hauch, Siegfried; Aktas, Bahriye; Tewes, Mitra; Kimmig, Rainer; Kasimir‐Bauer, Sabine

doi:10.1373/clinchem.2016.269605

Cited by 48 publications

(36 citation statements)

References 34 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…These data showed that the isolation of CTCs occurred in a specific manner and that the epithelial population isolated with the CellSearch ® approach was also harvested with this strategy. Furthermore, Bredemeier and colleagues described KRT19 as a powerful marker to identify CTCs in metastatic breast cancer (MBC) [31]. We also found that KRT19 was higher in luminal patients versus TNBC.…”

Section: Discussionsupporting

confidence: 62%

See 1 more Smart Citation

CTCs Expression Profiling for Advanced Breast Cancer Monitoring

Pereira-Veiga¹,

Martínez‐Fernández

Abuín³

et al. 2019

Cancers

View full text Add to dashboard Cite

The study of circulating tumor cells (CTCs) has a huge clinical interest in advance and metastatic breast cancer patients. However, many approaches are biased by the use of epithelial markers, which underestimate non-epithelial CTCs phenotypes. CTCs enumeration provides valuable prognostic information; however, molecular characterization could be the best option to monitor patients throughout the disease since it may provide more relevant clinical information to the physicians. In this work, we aimed at enumerating and performing a molecular characterization of CTCs from a cohort of 20 patients with metastatic breast cancer (MBC), monitoring the disease at different time points of the therapy, and at progression when it occurred. To this end, we used a CTC negative enrichment protocol that allowed us to recover a higher variety of CTCs phenotypes. With this strategy, we were able to obtain gene expression data from CTCs from all the patients. In addition, we found that high expression levels of PALB2 and MYC were associated with a worse outcome. Interestingly, we identified that CTCs with an EpCAMhighVIMlowALDH1A1high signature showed both shorter overall survival (OS) and progression-free survival (PFS), suggesting that CTCs with epithelial-stem features had the most aggressive phenotype.

show abstract

Section: Discussionsupporting

confidence: 62%

“…In this sense, some studies have explored CTCs in BC by using molecular methods [21][22][23][24][25][26][27][28]. However, only a few have evaluated the characteristics of CTCs after therapy [19,26,[29][30][31], and, to our knowledge, only one has used a negative enrichment approach comparable with ours [32].…”

Section: Discussionmentioning

confidence: 99%

CTCs Expression Profiling for Advanced Breast Cancer Monitoring

Pereira-Veiga¹,

Martínez‐Fernández

Abuín³

et al. 2019

Cancers

View full text Add to dashboard Cite

show abstract

“…Reijm et al, developed an 8-gene expression profile in CTCs which discriminates good and poor outcome to first-line aromatase inhibitors in MBC patients [37]. Bredemeier et al, also reported gene expression signatures in CTCs that can be used to monitor response to therapy in MBC [38]. It was also demonstrated that changed gene expression during first-line systemic therapy for MBC could be a possible explanation for treatment resistance [39].…”

Section: Changes In Expression; Reversible Re-programingmentioning

confidence: 99%

Circulating Tumor Cells in Early and Advanced Breast Cancer; Biology and Prognostic Value

Fabisiewicz

Szostakowska-Rodzoś

Żaczek

et al. 2020

IJMS

View full text Add to dashboard Cite

Breast cancer metastasis is the leading cause of cancer deaths in women and is difficult to combat due to the long periods in which disseminated cells retain a potential to be re-activated and start the relapse. Assessing the number and molecular profile of circulating tumor cells (CTCs) in breast cancer patients, especially in early breast cancer, should help in identifying the possibility of relapse in time for therapeutic intervention to prevent or delay recurrence. While metastatic breast cancer is considered incurable, molecular analysis of CTCs still have a potential to define particular susceptibilities of the cells representing the current tumor burden, which may differ considerably from the cells of the primary tumor, and offer more tailored therapy to the patients. In this review we inspect the routes to metastasis and how they can be linked to specific features of CTCs, how CTC analysis may be used in therapy, and what is the current status of the research and efforts to include CTC analysis in clinical practice.There are two main hypotheses describing cancer dissemination: linear progression, according to which, metastatic potential is gained gradually, and the whole process proceeds in steps and needs time, and parallel progression, according to which dissemination takes place early on, even before clinical manifestation of the tumor [6,7] (Figure 1). In the linear progression model, the evolving primary tumor gives rise to metastases due to increasingly aggressive and invasive phenotypes of the subclones of tumor cells. This model is in agreement with the postulated role of the epithelial-to-mesenchymal transition (EMT) in cancer and assumes active degradation of the stroma and migration into blood vessels by the motile, invasive single cells that broke loose from the epithelial monolayer. In contrast to that, parallel progression postulates intravasation by passive shedding, which may take place shortly after the angiogenic switch, occurring during the early, pre-invasive stage of tumor development [8,9].

show abstract

“…uPA is coded for by the Plasminogen Activator Urokinase ( PLAU ) gene and activates plasminogen via conversion to plasmin (Mahmood et al, ). Association between shear stress stimulus and the uPA system modulation has been shown for proximal tubular cells (Essig & Friedlander, ), endothelial cells (Diamond, Eskin, & McIntire, ; Dolan, Sim, Meng, & Kolega, ; Sokabe et al, ), and smooth muscle cells (Papadaki et al, ); although PLAU upregulation has been linked to metastatic cancers as a possible biomarker (Bredemeier et al, ; Sepiashvili et al, ; Tang & Han, ), it has yet to be directly tied to mechano‐stimulus in cancer.…”

Section: Introductionmentioning

confidence: 99%

Fluid shear stress stimulates breast cancer cells to display invasive and chemoresistant phenotypes while upregulating PLAU in a 3D bioreactor

Novak

Horst

Taylor

et al. 2019

Biotech & Bioengineering

View full text Add to dashboard Cite

Breast cancer cells experience a range of shear stresses in the tumor microenvironment (TME). However most current in vitro three‐dimensional (3D) models fail to systematically probe the effects of this biophysical stimuli on cancer cell metastasis, proliferation, and chemoresistance. To investigate the roles of shear stress within the mammary and lung pleural effusion TME, a bioreactor capable of applying shear stress to cells within a 3D extracellular matrix was designed and characterized. Breast cancer cells were encapsulated within an interpenetrating network hydrogel and subjected to shear stress of 5.4 dynes cm−2 for 72 hr. Finite element modeling assessed shear stress profiles within the bioreactor. Cells exposed to shear stress had significantly higher cellular area and significantly lower circularity, indicating a motile phenotype. Stimulated cells were more proliferative than static controls and showed higher rates of chemoresistance to the anti‐neoplastic drug paclitaxel. Fluid shear stress‐induced significant upregulation of the PLAU gene and elevated urokinase activity was confirmed through zymography and activity assay. Overall, these results indicate that pulsatile shear stress promotes breast cancer cell proliferation, invasive potential, chemoresistance, and PLAU signaling.

show abstract

Gene Expression Signatures in Circulating Tumor Cells Correlate with Response to Therapy in Metastatic Breast Cancer

Abstract: could be a key marker in distinguishing R from NR, and was powerful in identifying CTCs.

Cited by 48 publications

References 34 publications

CTCs Expression Profiling for Advanced Breast Cancer Monitoring

CTCs Expression Profiling for Advanced Breast Cancer Monitoring

Circulating Tumor Cells in Early and Advanced Breast Cancer; Biology and Prognostic Value

Fluid shear stress stimulates breast cancer cells to display invasive and chemoresistant phenotypes while upregulating PLAU in a 3D bioreactor

Contact Info

Product

Resources

About