scholarly journals Functional role of vitronectin in breast cancer

PLoS ONE ◽  
2020 ◽  
Vol 15 (11) ◽  
pp. e0242141
Author(s):  
Alakesh Bera ◽  
Madhan Subramanian ◽  
John Karaian ◽  
Michael Eklund ◽  
Surya Radhakrishnan ◽  
...  

Breast Cancer is the most common form of cancer in women worldwide, impacting nearly 2.1 million women each year. Identification of new biomarkers could be key for early diagnosis and detection. Vitronectin, a glycoprotein that is abundantly found in serum, extracellular matrix, and bone, binds to integrin αvβ3, and promotes cell adhesion and migration. Current studies indicate that patients with amplified vitronectin levels have lower survival rates than patients without amplified vitronectin levels. In this study, we focused on the role of vitronectin in breast cancer survival and its functional role as a non-invasive biomarker for early stage and stage specific breast cancer detection. To confirm that the expression of vitronectin is amplified in breast cancer, a total of 240 serum samples (n = 240), 200 from breast cancer patients and 40 controls were analyzed using the Reverse Phase Protein Array (RPPA) technique. Of the 240 samples, 120 samples were of African American (AA) descent, while the other 120 were of White American (WA) descent. Data indicated that there were some possible racial disparities in vitronectin levels and, differences also seen in the recurrent patient samples. Next, we tried to uncover the underlying mechanism which plays a critical role in vitronectin expression. The cellular data from four different breast cancer cell lines- MCF7, MDA-MB-231, MDA-MB-468, and HCC1599 indicated that the PI3K/AKT axis is modulating the expression of vitronectin. We believe that vitronectin concentration levels are involved and connected to the metastasis of breast cancer in certain patients, specifically based on recurrence or ethnicity, which is detrimental for poor prognosis. Therefore, in this current study we showed that the serum vitronectin levels could be an early marker for the breast cancer survival and we also determine the cellular signaling factors which modulate the expression and concentration of vitronectin.

2017 ◽  
Vol 35 (7_suppl) ◽  
pp. 115-115
Author(s):  
Joseph Fabre ◽  
Jérôme Giustiniani ◽  
Stéphanie Servagi-Vernat ◽  
Christian Garbar ◽  
Yacine Merrouche ◽  
...  

115 Background: Inflammation has been known to play a critical role in cancer for decades. Tumors build up on the “inflammatory soup” in the surrounding microenvironment to progress, grow, metastasize and evade immune response. Since its discovery in the nineties, interleukin-17 (IL-17A), a proinflammatory cytokine mainly secreted by T helper 17 cells, has been extensively studied in chronic inflammatory diseases like psoriasis or rheumatoid arthritis. In solid malignancies, there is growing evidence that IL-17 enhances cancer cells’ capacity of division, invasion and chemotherapy resistance. Methods: Based on our team's experience and publications, we systematically reviewed the existing literature about the role of IL-17 in cancers, in aim to discuss if developing IL-17 pathway-targeting strategies could be effective. Results: Data from several preclinical studies indicated tumor-promoting effects of IL-17 on diverse cancer models, cellular or murine. In clinical studies, detection of high levels of IL-17 in patients’ blood or tumors was correlated to bad prognosis. Concordantly, we reported recently in triple negative breast cancer cell lines that IL-17A and IL-17E promoted resistance to Docetaxel and failed to induce apoptosis as previously observed for IL-17E by other authors. Interestingly, we also revealed that both cytokines induced the generation of tumorigenic low molecular weight forms of cyclin E (LMW-E), which high levels correlated strongly with a poor survival in breast cancer patients. Lastly, we reported a crosstalk between IL-17E and epidermal growth factor signaling, which confers in vitro resistance to EGFR-targeted therapies. In opposition, a few studies observed that IL-17 inhibited tumor grafts development and metastasis in rodent possibly through the expression of other proinflammatory mediators such as IL-1β, TNFα, IL-6 or GM-CSF and the recruitment of neutrophils to the tumor site. Conclusions: Most of the literature supports a critical role of IL-17 in cancer promotion and development. These results encourage us to present the IL-17 family members and their receptors as potent targets for anticancer biotherapy.


2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Eui Jung Moon ◽  
Stephano S. Mello ◽  
Caiyun G. Li ◽  
Jen-Tsan Chi ◽  
Kaushik Thakkar ◽  
...  

AbstractHypoxia plays a critical role in tumor progression including invasion and metastasis. To determine critical genes regulated by hypoxia that promote invasion and metastasis, we screen fifty hypoxia inducible genes for their effects on invasion. In this study, we identify v-maf musculoaponeurotic fibrosarcoma oncogene homolog F (MAFF) as a potent regulator of tumor invasion without affecting cell viability. MAFF expression is elevated in metastatic breast cancer patients and is specifically correlated with hypoxic tumors. Combined ChIP- and RNA-sequencing identifies IL11 as a direct transcriptional target of the heterodimer between MAFF and BACH1, which leads to activation of STAT3 signaling. Inhibition of IL11 results in similar levels of metastatic suppression as inhibition of MAFF. This study demonstrates the oncogenic role of MAFF as an activator of the IL11/STAT3 pathways in breast cancer.


PLoS ONE ◽  
2014 ◽  
Vol 9 (2) ◽  
pp. e87610 ◽  
Author(s):  
Jan Blancato ◽  
Ashley Graves ◽  
Banafsheh Rashidi ◽  
Maria Moroni ◽  
Leopold Tchobe ◽  
...  

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Hassan Nasrollahpour ◽  
Abdolhossein Naseri ◽  
Mohammad-Reza Rashidi ◽  
Balal Khalilzadeh

AbstractBiopolymer films have drawn growing demand for their application in the point of care domain owing to their biocompatibility, eco-friendly, and eligibility for in vivo analyses. However, their poor conductivity restricts their sensitivity in diagnostics. For high-quality electrochemical biosensor monitoring, two vital factors to be greatly paid attention are the effective merge of amplification modifiers with transducing surface and the superior linking across the recognition interface. Here, we introduce an enzyme-free electrochemical biosensor based on electrosynthesized biocompatible WO3/poly glutamic acid nano-biocomposites to address the hardships specific to the analysis of circulating proteins clinical samples. In addition to its green synthesis route, the poor tendency of both components of the prepared nano-biocomposite to amine groups makes it excellent working in untreated biological samples with high contents of proteins. Several electrochemical and morphological investigations (SEM, EDX, and dot mapping) were fulfilled to gain a reliable and trustful standpoint of the framework. By using this nanobiosensor, the concentration of HER-2 was detectable as low as 1 fg mL−1 with a wide linear response between 1 ng mL−1 and 1 fg mL−1. Meanwhile, the protocol depicted ideal specificity, stability, and reproducibility for the detection of HER-2 protein in untreated serum samples of breast cancer patients.


Author(s):  
Peter A. van Dam ◽  
Cary Kaufman ◽  
Carlos Garcia-Etienne ◽  
Marie-Jeanne Vrancken Peeters ◽  
Robert Mansel

Abstract: The role of the surgeon managing breast diseases has been the subject of continuous evolution, moving from the cancer-extirpative surgeon to a deeply informed surgical leader, who interacts in a multidisciplinary setting also encompassing tasks for risk assessment, genetic counselling, and new diagnostic approaches. Surgical removal of the tumour remains the cornerstone in treating early stage breast cancer. During the last century, breast cancer surgery became less radical, breast-conserving treatment emerged, and the role of axillary lymphadenectomy changed from a therapeutic procedure into a staging procedure with prognostic implications. Later, the sentinel node concept reduced the need for complete axillary clearance in most cases. Nowadays, thanks to breast-conserving surgery, oncoplastic techniques, and reconstructive procedures, most breast cancer patients can overcome this disease without serious permanent physical mutilation. A multidisciplinary approach, benchmarking, and quality assurance have improved outcomes markedly.


2019 ◽  
Vol 20 (5) ◽  
pp. 1237 ◽  
Author(s):  
Bhawna Sharma ◽  
Kalyan Nannuru ◽  
Sugandha Saxena ◽  
Michelle Varney ◽  
Rakesh Singh

Most breast cancer patients die due to bone metastasis. Although metastasis accounts for 5% of the breast cancer cases, it is responsible for most of the deaths. Sometimes even before the detection of a primary tumor, most of the patients have bone and lymph node metastasis. Moreover, at the time of death, breast cancer patients have the bulk of the tumor burden in their bones. Therapy options are available for the treatment of primary tumors, but there are minimal options for treating breast cancer patients who have bone metastasis. C-X-C motif chemokine receptor type 2 (CXCR2) receptor-mediated signaling has been shown to play a critical role during bone-related inflammations and its ligands C-X-C motif chemokine ligand 6 (CXCL6) and 8 (CXCL8) aid in the resorption of bone during bone metastasis. In this study, we tested the hypothesis that CXCR2 contributes to mammary tumor-induced osteolysis and bone metastasis. In the present study, we examined the role of both tumor cell-derived and host-derived CXCR2 in influencing mammary tumor cell bone metastasis. For understanding the role of tumor cell-derived CXCR2, we utilized Cl66 CXCR2 knockdown (Cl66-shCXCR2) and Cl66-Control cells (Cl66-Control) and observed a significant decrease in tumor growth and tumor-induced osteolysis in Cl66-shCXCR2 cells in comparison with the Cl66-Control cells. Next, for understanding the role of host-derived CXCR2, we utilized mice with genomic knockdown of CXCR2 (Cxcr2−/−) and injected Cl66-Luciferase (Cl66-Luc) or 4T1-Luciferase (4T1-Luc) cells. We observed decreased bone destruction and metastasis in the bone of Cxcr2−/− mice. Our data suggest the importance of both tumor cell- and host-derived CXCR2 signaling in the bone metastasis of breast cancer cells.


2019 ◽  
Vol 79 (02) ◽  
pp. 184-188 ◽  
Author(s):  
Carsten Gründker ◽  
Matthias Läsche ◽  
Johanna Hellinger ◽  
Günter Emons

AbstractTumour metastasis is responsible for more than 90% of tumour-associated mortality. About one third of breast cancer patients in the early stage develop metastases. The transformation in tumour development referred to as the “metastatic cascade” or “metastatic cycle” is a complex and multi-stage event. While it is generally recognised that epithelial-mesenchymal transformation (EMT) plays a crucial role in cancer progression and metastasis, the metabolic events in this process have received little attention to date. We would therefore like to provide a brief overview here of the influence of the metabolism on the progression and metastasis of tumours.


BMC Cancer ◽  
2012 ◽  
Vol 12 (1) ◽  
Author(s):  
Kate M Peters ◽  
Stacey L Edwards ◽  
Shalima S Nair ◽  
Juliet D French ◽  
Peter J Bailey ◽  
...  

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