1,720,968 research outputs found
miRNAs in melanoma: a defined role in tumor progression and metastasis
No full textThe crosstalk of melanoma cells with components of the microenvironment promotes malignant cell proliferation and spread to distant tissues. Although the major pathogenetic events have already been elucidated, the mechanisms that drive the metastatic behavior of tumor cells are still undefined. MicroRNAs (miRNAs) are small non-coding RNAs that control post-transcriptional gene expression through interconnected kinases upstream of functional genes involved in tumor progression. Here, we review the biological relevance of melanoma-related miRNAs and focus on their potential role in propagating signals that may cause tumor microenvironment rearrangements, as well as disablement of the immune system and melanoma cell proliferation
Tumor-derived exosomes promote the in vitro osteotropism of melanoma cells by activating the SDF-1/CXCR4/CXCR7 axis.
Full text linkBackground: Bone metastases occur rarely in patients sufering from malignant melanoma, although their onset severely worsens both prognosis and quality of life. Extracellular vesicles (EVs) including exosomes (Exos) are active players in melanoma progression involved in the formation of the pre-metastatic niche.
Methods: Trans-well assays explored the basal migratory and invasive potential of four melanoma cell lines and investigated their diferent propensity to be attracted toward the bone. Exosomes were purifed from cell supernatants by ultracentrifugation and explored in their ability to infuence the bone tropism of melanoma cells. The molecular machinery activated during this process was investigated by RT-PCR, droplet digital-PCR, fow-cytometry
and Western blot, while loss of function studies with dedicated siRNAs defned the single contribute of CXCR4 and CXCR7 molecules.
Results: Melanoma cells revealed a variable propensity to be attracted toward bone fragments. Gene profling of both osteotropic and not-osteotropic cells did not show a diferent expression of those genes notoriously correlated to chemotaxis and bone metastasis. However, bone conditioned medium signifcantly increased CXCR4, CXCR7 and PTHrP expression solely to osteotropic cells, while their Exos were able to revert the original poor bone tropism of notosteotropic cells through CXCR7 up-regulation. Silencing experiments also demonstrated that membrane expression of CXCR7 is required by melanoma cells to promote their chemotaxis toward SDF-1 gradients.
Conclusions: Our data correlated the osteotropism of melanoma cells to the activation of the SDF-1/CXCR4/CXCR7 axis following the exposition of tumor cells to bone-derived soluble factors. Also, we demonstrated in vitro that tumor-derived Exos can reprogram the innate osteotropism of melanoma cells by up-regulating membrane CXCR7. These results may have a potential translation to future identifcation of druggable targets for the treatment of skeletal
metastases from malignant melanoma
Immune System Evasion as Hallmark of Melanoma Progression: The Role of Dendritic Cells.
Full text linkMelanoma is an immunogenic tumor whose relationship with immune cells resident in the microenvironment significantly influences cancer cell proliferation, progression, and metastasis. During melanomagenesis, both immune and melanoma cells undergo the immunoediting process that includes interconnected phases as elimination, equilibrium, and escape or immune evasion. In this context, dendritic cells (DCs) are active players that indirectly counteract the proliferation of melanoma cells. Moreover, DC maturation, migration, and cross-priming as well as their functional interplay with cytotoxic T-cells through ligands of immune checkpoint receptors result impaired. A number of signals propagated by highly proliferating melanoma cells and accessory cells as T-cells, natural killer cells (NKs), tumor-associated macrophages (TAMs), T-regulatory cells (T-regs), myeloid-derived suppressor cells (MDSCs), and endothelial cells participate to create an immunosuppressive milieu that results engulfed of tolerogenic factors and interleukins (IL) as IL-6 and IL-10. To underline the role of the immune infiltrate in blocking the melanoma progression, it has been described that the composition, density, and distribution of cytotoxic T-cells in the surrounding stroma is predictive of responsiveness to immunotherapy. Here, we review the major mechanisms implicated in melanoma progression, focusing on the role of DCs
Circulating dendritic cell levels identify high-risk stage II-III melanoma patients: a potential role as additional prognostic marker.
No full text
Going Beyond Counting First Authors in Author Co-citation Analysis
Full text linkThe present study examines one of the fundamental aspects of author co-citation analysis (ACA) - the way co-citation
counts are defined. Co-citation counting provides the data on which all subsequent statistical analyses and mappings
are based, and we compare ACA results based on two different types of co-citation counting - the traditional type that
only counts the first one among a cited work's authors on the one hand and a non-traditional type that takes into
account the first 5 authors of a cited work on the other hand. Results indicate that the picture produced through this non-traditional author co-citation counting contains more coherent author groups and is therefore considerably clearer. However, this picture represents fewer specialties in the research field being studied than that produced through the traditional first-author co-citation counting when the same number of top-ranked authors is selected and analyzed. Reasons for these effects are discussed
Dual-procedural separation of CTCs in cutaneous melanoma provides useful information for both molecular diagnosis and prognosis
Full text linkBackground: Circulating tumor cells (CTCs) have recently emerged as a new dynamic soluble marker for several malignancies including cutaneous melanoma (CM) and are suitable for prognostic evaluations and treatment monitoring. However, to date many limitations still hamper the wide-scale application of CTCs in CM setting, including the lack of standardized methods as well as both low levels and heterogeneity of these cells. Methods: We developed a protocol for CTC detection in CM based on immune-magnetic sorting to deplete CD45-, CD31- or CD34-positive cells, followed by dielectrophoretic DEPArray separation according to cell morphology and immunophenotype. To this end, we explored the expression of melanoma stem cell antigens (CD271, ABCB5, and RANK) and the epithelial-to-mesenchymal transition markers (N-Cad, -CD44, and -MCAM/CD146) on CTCs from 17 stage IV CM patients, and investigated their BRAF mutational status by droplet digital PCR. Results: The number of CTCs isolated from CM patients ranged from 2 to 91 cells (38 ± 6.4) with respect to healthy donors (p < 0.0002). To confirm the melanoma origin of isolated cells, we observed an 80% agreement between their BRAFV600 mutational status and matched primary tumors. The characterization of the immune phenotype of isolated cells revealed high interindividual and intraindividual heterogeneity that was found to correlate with the clinical outcome. Conclusions: The dual-step protocol of immune-magnetic sorting and subsequent dielectrophoretic DEPArray separation, turned out to be a suitable method to isolate viable CTCs from stage IV melanoma patients and enabled quantitative and qualitative analyses on these cells, which may deserve prospective evaluation for potential use in the clinical practice
Revisiting the Role of Exosomes in Colorectal Cancer: Where Are We Now?
Full text linkExosomes (Exos) are nano-sized extracellular vesicles constitutively released by both prokaryotic and eukaryotic cells. Their role as intercellular messengers involved in both physiological and pathological processes has overwhelmingly come to light in the last decade, and their contribution to cancerogenesis and tumor metastasis is under intensive investigation. Here we review the most recent information concerning Exos in colorectal cancer (CRC) and focus on their effects on tumor microenvironment and the immune system, as well as unravel their role in the formation of the pre-metastatic niche and in drug resistance. Such a recent knowledge on Exos depicts their potential translations into the clinical arena, either as an alternative tool of “liquid biopsy” or novel therapeutic approaches for CRC. However, due to the limited data available from clinical trials, they need further validations before addressing their putative application in oncology
Large extracellular vesicles—a new frontier of liquid biopsy in oncology
Full text linkExtracellular Vesicles (EVs) are emerging as pivotal elements in cancer. Many studies have focused on the role of Small-(S)-EVs but in recent years Large-(L)-EVs have progressively gained increasing interest due to their peculiar content and functions. Tumor-derived L-EVs carry a lot of oncogenic proteins, nucleic acids and lipids to recipient cells and are involved in the reshaping of the tumor microenvironment as well as in the metabolic rewiring and the promotion of the pro-metastatic attitude of cancer cells. Several techniques have been developed for the isolation of L-EVs and commercial kits are also available for efficient and easy recovery of these vesicles. Also, the improvement in DNA sequencing and “omics sciences” profoundly changed the way to analyze and explore the molecular content of L-EVs, thus providing novel and potentially useful cancer biomarkers. Herein, we review the most recent findings concerning the role of L-EVs in cancer and discuss their possible use in oncology as “liquid biopsy” tools as compared to the other classes of EVs
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