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    Caveolin-1-dependent tenascin C inclusion in extracellular vesicles is required to promote breast cancer cell malignancy
    (2023)
    America Campos
    ;
    Renato Burgos-Ravanal
    ;
    Lorena Lobos-González
    ;
    Ricardo Huilcamán
    ;
    María Fernanda González
    <jats:p> Background: Elevated expression of CAV1 in breast cancer increases tumor progression. Extracellular vesicles (EVs) from CAV1-expressing MDA-MB-231 breast cancer cells contain Tenascin C (TNC), but the relevance of TNC remained to be defined. Methods: EVs were characterized by nanotracking analysis, microscopy and western blotting. The uptake of EVs by cells was studied using flow cytometry. The effects of EVs on breast cancer cells were tested in migration, invasion, colony formation and in vivo assays. Results: EVs were taken up by cells; however, only those containing TNC promoted invasiveness. In vivo, EVs lacking TNC ceased to promote tumor growth. Conclusion: CAV1 and TNC contained in breast cancer cell-derived EVs were identified as proteins that favor progression of breast cancer. </jats:p>
    Scopus© Citations 7  1
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    CRISPR/Cas13-Based Platforms for a Potential Next-Generation Diagnosis of Colorectal Cancer through Exosomes Micro-RNA Detection: A Review
    (2021)
    Benjamín Durán-Vinet
    ;
    Karla Araya-Castro
    ;
    ;
    Luis Vergara
    ;
    Helga Weber
    <jats:p>Colorectal cancer (CRC) is the third most prevalent cancer with the second highest mortality rate worldwide. CRC is a heterogenous disease with multiple risk factors associated, including obesity, smoking, and use of alcohol. Of total CRC cases, 60% are diagnosed in late stages, where survival can drop to about 10%. CRC screening programs are based primarily on colonoscopy, yet this approach is invasive and has low patient adherence. Therefore, there is a strong incentive for developing molecular-based methods that are minimally invasive and have higher patient adherence. Recent reports have highlighted the importance of extracellular vesicles (EVs), specifically exosomes, as intercellular communication vehicles with a broad cargo, including micro-RNAs (miRNAs). These have been syndicated as robust candidates for diagnosis, primarily for their known activities in cancer cells, including immunoevasion, tumor progression, and angiogenesis, whereas miRNAs are dysregulated by cancer cells and delivered by cancer-derived exosomes (CEx). Quantitative polymerase chain reaction (qPCR) has shown good results detecting specific cancer-derived exosome micro-RNAs (CEx-miRNAs) associated with CRC, but qPCR also has several challenges, including portability and sensitivity/specificity issues regarding experiment design and sample quality. CRISPR/Cas-based platforms have been presented as cost-effective, ultrasensitive, specific, and robust clinical detection tools in the presence of potential inhibitors and capable of delivering quantitative and qualitative real-time data for enhanced decision-making to healthcare teams. Thereby, CRISPR/Cas13-based technologies have become a potential strategy for early CRC diagnosis detecting CEx-miRNAs. Moreover, CRISPR/Cas13-based platforms’ ease of use, scalability, and portability also showcase them as a potential point-of-care (POC) technology for CRC early diagnosis. This study presents two potential CRISPR/Cas13-based methodologies with a proposed panel consisting of four CEx-miRNAs, including miR-126, miR-1290, miR-23a, and miR-940, to streamline novel applications which may deliver a potential early diagnosis and prognosis of CRC.</jats:p>
      7Scopus© Citations 22
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    Antibacterial Effect of Honey-Derived Exosomes Containing Antimicrobial Peptides Against Oral Streptococci
    (2021)
    Camila Leiva-Sabadini
    ;
    Simon Alvarez
    ;
    Nelson P Barrera
    ;
    Christina MAP Schuh
    ;
    Sebastian Aguayo
    Scopus© Citations 39  3
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    New Perspectives to Improve Mesenchymal Stem Cell Therapies for Drug-Induced Liver Injury
    <jats:p>Drug-induced liver injury (DILI) is one of the leading causes of acute liver injury. Many factors may contribute to the susceptibility of patients to this condition, making DILI a global medical problem that has an impact on public health and the pharmaceutical industry. The use of mesenchymal stem cells (MSCs) has been at the forefront of regenerative medicine therapies for many years, including MSCs for the treatment of liver diseases. However, there is currently a huge gap between these experimental approaches and their application in clinical practice. In this concise review, we focus on the pathophysiology of DILI and highlight new experimental approaches conceived to improve cell-based therapy by the in vitro preconditioning of MSCs and/or the use of cell-free products as treatment for this liver condition. Finally, we discuss the advantages of new approaches, but also the current challenges that must be addressed in order to develop safer and more effective procedures that will allow cell-based therapies to reach clinical practice, enhancing the quality of life and prolonging the survival time of patients with DILI.</jats:p>
    Scopus© Citations 10  1
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    Lactadherin: From a Well-Known Breast Tumor Marker to a Possible Player in Extracellular Vesicle-Mediated Cancer Progression
    (2022)
    Eduardo Durán-Jara
    ;
    Tamara Vera-Tobar
    ;
    Lorena De Lourdes Lobos-González
    <jats:p>Lactadherin is a secreted glycoprotein associated with the milk fat globule membrane, which is highly present in the blood and in the mammary tissue of lactating women. Several biological functions have been associated with this protein, mainly attributable to its immunomodulatory role promoting phagocyte-mediated clearance of apoptotic cells. It has been shown that lactadherin also plays important roles in cell adhesion, the promotion of angiogenesis, and tissue regeneration. On the other hand, this protein has been used as a marker of breast cancer and tumor progression. Recently, high levels of lactadherin has been associated with poor prognosis and decreased survival, not only in breast cancer, but also in melanoma, ovarian, colorectal, and other types of cancer. Although the mechanisms responsible for the tumor-promoting effects attributed to lactadherin have not been fully elucidated, a growing body of literature indicates that lactadherin could be a promising therapeutic target and/or biomarker for breast and other tumors. Moreover, recent studies have shown its presence in extracellular vesicles derived from cancer cell lines and cancer patients, which was associated with cancer aggressiveness and worse prognosis. Thus, this review will focus on the link between lactadherin and cancer development and progression, its possible use as a cancer biomarker and/or therapeutic target, concluding with a possible role of this protein in cellular communication mediated by extracellular vesicles</jats:p>
    Scopus© Citations 14  4
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    Antioxidant Biomolecules and Their Potential for the Treatment of Difficult-to-Treat Depression and Conventional Treatment-Resistant Depression
    <jats:p>Major depression is a devastating disease affecting an increasing number of people from a young age worldwide, a situation that is expected to be worsened by the COVID-19 pandemic. New approaches for the treatment of this disease are urgently needed since available treatments are not effective for all patients, take a long time to produce an effect, and are not well-tolerated in many cases; moreover, they are not safe for all patients. There is solid evidence showing that the antioxidant capacity is lower and the oxidative damage is higher in the brains of depressed patients as compared with healthy controls. Mitochondrial disfunction is associated with depression and other neuropsychiatric disorders, and this dysfunction can be an important source of oxidative damage. Additionally, neuroinflammation that is commonly present in the brain of depressive patients highly contributes to the generation of reactive oxygen species (ROS). There is evidence showing that pro-inflammatory diets can increase depression risk; on the contrary, an anti-inflammatory diet such as the Mediterranean diet can decrease it. Therefore, it is interesting to evaluate the possible role of plant-derived antioxidants in depression treatment and prevention as well as other biomolecules with high antioxidant and anti-inflammatory potential such as the molecules paracrinely secreted by mesenchymal stem cells. In this review, we evaluated the preclinical and clinical evidence showing the potential effects of different antioxidant and anti-inflammatory biomolecules as antidepressants, with a focus on difficult-to-treat depression and conventional treatment-resistant depression.</jats:p>
    Scopus© Citations 57  1
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    Cell Intrinsic and Extrinsic Mechanisms of Caveolin-1-Enhanced Metastasis
    (2019)
    America Campos
    ;
    Renato Burgos-Ravanal
    ;
    Maria Fernanda Gonzalez
    ;
    Ricardo Huilcaman
    ;
    <jats:p>Caveolin-1 (CAV1) is a scaffolding protein with a controversial role in cancer. This review will initially discuss earlier studies focused on the role as a tumor suppressor before elaborating subsequently on those relating to function of the protein as a promoter of metastasis. Different mechanisms are summarized illustrating how CAV1 promotes such traits upon expression in cancer cells (intrinsic mechanisms). More recently, it has become apparent that CAV1 is also a secreted protein that can be included into exosomes where it plays a significant role in determining cargo composition. Thus, we will also discuss how CAV1 containing exosomes from metastatic cells promote malignant traits in more benign recipient cells (extrinsic mechanisms). This ability appears, at least in part, attributable to the transfer of specific cargos present due to CAV1 rather than the transfer of CAV1 itself. The evolution of how our perception of CAV1 function has changed since its discovery is summarized graphically in a time line figure.</jats:p>
      1  2Scopus© Citations 52
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    Exosomes on the border of species and kingdom intercommunication
    (2019) ;
    Jimena Cuenca
    ;
    Francisca Alcayaga-Miranda
    ;
    Maroun Khoury
      1Scopus© Citations 48  4
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    Extracellular Vesicles as Biomarkers for the Detection of a Tumor Marker Gene in Epidermolysis Bullosa-Associated Squamous Cell Carcinoma
    (2018)
    Yuchen Sun
    ;
    Katharina Woess
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    Melanie Kienzl
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    Victoria M. Leb-Reichl
    ;
    Andrea Feinle
      1Scopus© Citations 13
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    Subclinical Detection of Diabetic Cardiomyopathy with MicroRNAs: Challenges and Perspectives
    (2016)
    Luis E. León
    ;
    Sweta Rani
    ;
    Mauricio Fernandez
    ;
    Martín Larico
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    SEBASTIAN DANTE CALLIGARIS CAPRIOGLIO
    <jats:p>The prevalence of cardiac diabetic diseases has been increased around the world, being the most common cause of death and disability among diabetic patients. In particular, diabetic cardiomyopathy is characterized with a diastolic dysfunction and cardiac remodelling without signs of hypertension and coronary artery diseases. In an early stage, it is an asymptomatic disease; however, clinical studies demonstrate that diabetic myocardia are more vulnerable to injury derived by acute myocardial infarct and are the worst prognosis for rehabilitation. Currently, biochemical and imaging diagnostic methods are unable to detect subclinical manifestation of the disease (prior to diastolic dysfunction). In this review, we elaborately discuss the current scientific evidences to propose circulating microRNAs as promising biomarkers for early detection of diabetic cardiomyopathy and, then, to identify patients at high risk of diabetic cardiomyopathy development. Moreover, here we summarise the research strategies to identify miRNAs as potential biomarkers, present limitations, challenges, and future perspectives.</jats:p>
      4Scopus© Citations 44