scholarly journals ADRENOMEDULIN DI KARSINOMA PAYUDARA DENGAN METASTASIS

Author(s):  
Stefanus Lembar

Metastasis is the leading cause of mortality in patients with breast cancer. The molecular biology behind the metastasis is verycomplex and may require changes in the regulation of the cell cycle, protein that promotes autocrine growth loop, and the protein thatcauses epithelial to mesenchymal transition. More complex, it is clear that the biology of metastasis is partly governed by the non-tumourcells, including fibroblasts, endothelial cells and myoepithelial cells. Adrenomedullin is an autocrine growth factor produced by the renalcarcinoma cells. However, previous studies indicated that adrenomedullin can be secreted in various carcinoma tissue and carcinoma cells.Adrenomedullin may mediate immunosuppression, antiapoptosis, angiogenesis and proliferation, thus it is an important tumour cellsurvival factor underlying human carcinoma genesis. The role of adrenomedullin in the carcinoma genesis, invasion and metastasis hasbeen greatly focused. The aim of this study was to determine the concentration of adrenomedullin in patients with metastatic breast cancer.A total of 64 patients with breast cancer aged 21–90 years (63 women and 1 man) in Jakarta has been participated in this study aftersigning informed consent. Metastasis was confirmed by examination of bone scanning. Concentrations of adrenomedullin were measuredby EnzymeLinked Immunosorbent Assay (ELISA) using a commercial kit. Based on examination of bone scanning, there were 24 (37.5%)subjects with metastasis and 40 (62.5%) nonmetastasis. Mean of the concentrations of adrenomedullin in the subjects with metastasiswas 252.5 (205.0–299.9) pg/mL, while in the nonmetastasis was 203.1 (178.7–227.5) pg/mL. The concentrations of adrenomedullinwere significantly higher in subjects with metastasis than nonmetastasis (p=0.041). High concentration of adrenomedullin in the subjectswith metastasis suggests that adrenomedullin may be more likely to be involved in metastasis.

2021 ◽  
Vol 10 (4) ◽  
pp. 684
Author(s):  
Lorena Alexandra Lisencu ◽  
Eduard-Alexandru Bonci ◽  
Alexandru Irimie ◽  
Ovidiu Balacescu ◽  
Cosmin Lisencu

Breast cancer is the most frequent form of cancer among women and is one of the leading causes of death. Two routes of the metastatic process have been described: linear and parallel progression. A key factor is represented by circulating tumor cells (CTCs). CTCs detach from the primary tumor or develop from cancer stem cells (CSCs) that undergo epithelial-to-mesenchymal transition (EMT). CTCs migrate to the distant site where the reverse process occurs and a new tumor arises. One of the key problems of metastatic disease is chemoresistance, which leads to treatment failure and, eventually, death. The aim of this review is to present up-to-date data regarding the role of CTCs in chemoresistance in metastatic breast cancer (MBC) patients. A search in Cochrane Library and MEDLINE databases was performed. A total of 125 articles were identified. The results of the final 12 eligible studies revealed that CTCs having stem cell features and those with mesenchymal features are aggressive subtypes of cells that survive chemotherapy, being responsible for chemoresistance and thus for disease progression in MBC patients. The hemodynamic shear stress, alongside dynamic changes among CTCs during the disease, is also an important disease progression factor.


Author(s):  
Vasileios Vardas ◽  
Eleni Politaki ◽  
Evangelia Pantazaka ◽  
Vassilis Georgoulias ◽  
Galatea Kallergi

Detection and characterization of circulating tumor cells (CTCs) with an epithelial-to-mesenchymal transition (EMT) phenotype is very important as it can contribute to the identification of high-risk for relapse and death patients. However, most of the methods are underestimating CTC numbers, due to their dependence on epithelial markers. In the current study, we evaluated the EMT phenotype in CTCs isolated from breast cancer (BC) patients, using the CellSearch system. Spiking experiments for the evaluation of the specificity and sensitivity of our method were performed using HeLa cells. Sixty-five breast cancer (BC) patients (47 early and 18 metastatic) were enrolled in the study. Vimentin is a mesenchymal marker which indicates tumoral cells acquiring invasive and malignant properties. We studied the vimentin (VIM) expression using the extra channel of the CellSearch system and an anti-vimentin antibody conjugated with FITC. In our present results, we reported the percentage of circulating tumor cells that expressed vimentin in early and in metastatic breast cancer patients. Interestingly, the incidence of cells with a CK-VIM+CD45- phenotype was detected in both settings. These cells were detected in 31.4% of CK-negative (11/35) and 82.3% of CK-positive (10/12) early BC patients. The corresponding numbers for metastatic disease were 15.4% (2/13) and 100% (5/5), respectively. Our results suggest that in CTC-negative patients, potentially undetectable tumor cells could be identified using the FDA-approved CellSearch system, based on the (CK-VIM+CD45-)-phenotype, offering additional information regarding the metastatic dissemination in cancer patients. Further experiments evaluating more biomarkers are necessary to elucidate the mechanisms that regulate tumorigenesis and metastasis.


2021 ◽  
Author(s):  
Nastaran Ghahhari ◽  
Magdalena Sznurkowska ◽  
Nicolas Hulo ◽  
Lilia Bernasconi ◽  
Nicola Aceto ◽  
...  

Abstract The epithelial to mesenchymal transition (EMT) has been proposed to contribute to the metastatic spread of breast cancer cells. EMT-promoting transcription factors determine a continuum of different EMT states. In contrast, estrogen receptor α (ERα) helps to maintain the epithelial phenotype of breast cancer cells and its expression is crucial for effective endocrine therapies. Determining whether and how EMT-associated transcription factors such as ZEB1 modulate ERα signaling during early stages of EMT could promote the discovery of novel therapeutic approaches to suppress metastasis. We have discovered that, shortly after induction of EMT and while cells are still epithelial, ZEB1 modulates ERα-mediated transcription induced by estrogen or cAMP signaling in breast cancer cells. Based on these findings and our ex vivo and xenograft results, we suggest that the functional interaction between ZEB1 and ERα may alter the tissue tropism of metastatic breast cancer cells towards bone.


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