1. Heterogeneous glioblastoma cell cross-talk promotes phenotype alterations and enhanced drug resistanceAna Koren, Helena Motaln, Živa Ramšak, Kristina Gruden, Christian Schichor, Tamara Lah Turnšek, 2015, original scientific article Abstract: Glioblastoma multiforme is the most lethal of brain cancer, and it comprises a heterogeneous mixture of functionally distinct cancer cells that affect tumor progression. We examined the U87, U251, and U373 malignant cell lines as in vitro models to determine the impact of cellular cross-talk on their phenotypic alterations in co-cultures. These cells were also studied at the transcriptome level, to define the mechanisms of their observed mutually affected genomic stability, proliferation, invasion and resistance to temozolomide. This is the first direct demonstration of the neural and mesenchymal molecular fingerprints of U87 and U373 cells, respectively. U87-cell conditioned medium lowered the genomic stability of U373 (U251) cells, without affecting cell proliferation. In contrast, upon exposure of U87 cells to U373 (U251) conditioned medium, U87 cells showed increased genomic stability, decreased proliferation rates and increased invasion, due to a plethora of produced cytokines identified in the co-culture media. This cross talk altered the expression 264 genes in U87 cells that are associated with proliferation, inflammation, migration, and adhesion, and 221 genes in U373 cells that are associated with apoptosis, the cell cycle, cell differentiation and migration. Indirect and direct co-culturing of U87 and U373 cells showed mutually opposite effects on temozolomide resistance. In conclusion, definition of transcriptional alterations of distinct glioblastoma cells upon co-culturing provides better understanding of the mechanisms of glioblastoma heterogeneity, which will provide the basis for more informed glioma treatment in the future.
Keywords: glioblastoma heterogeneity, U87 cells, temozolomide resistance, cellular cross-talk, transcriptomics
Published in DiRROS: 29.07.2024; Views: 719; Downloads: 380
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2. Mesenchymal stem cells differentially affect the invasion of distinct glioblastoma cell linesBarbara Breznik, Helena Motaln, Miloš Vittori, Ana Rotter, Tamara Lah Turnšek, 2017, original scientific article Abstract: Glioblastoma multiforme are an aggressive form of brain tumors that are characterized by distinct invasion of single glioblastoma cells, which infiltrate the brain parenchyma. This appears to be stimulated by the communication between cancer and stromal cells. Mesenchymal stem cells (MSCs) are part of the glioblastoma microenvironment, and their ‘cross-talk’ with glioblastoma cells is still poorly understood. Here, we examined the effects of bone marrow-derived MSCs on two different established glioblastoma cell lines U87 and U373. We focused on mutual effects of direct MSC/glioblastoma contact on cellular invasion in three-dimensional invasion assays in vitro and in a zebrafish embryo model in vivo. This is the first demonstration of glioblastoma cell-type-specific responses to MSCs in direct glioblastoma co-cultures, where MSCs inhibited the invasion of U87 cells and enhanced the invasion of U373. Inversely, direct cross-talk between MSCs and both of glioblastoma cell lines enhanced MSC motility. MSC-enhanced invasion of U373 cells was assisted by overexpression of proteases cathepsin B, calpain1, uPA/uPAR, MMP-2, -9 and -14, and increased activities of some of these proteases, as determined by the effects of their selective inhibitors on invasion. In contrast, these proteases had no effect on U87 cell invasion under MSC co-culturing. Finally, we identified differentially expressed genes, in U87 and U373 cells that could explain different response of these cell lines to MSCs. In conclusion, we demonstrated that MSC/glioblastoma cross-talk is different in the two glioblastoma cell phenotypes, which contributes to tumor heterogeneity.
Keywords: glioblastoma multiforme, proteases, mesenchymal stem cells, tumor heterogeneity, zebrafish model
Published in DiRROS: 24.07.2024; Views: 550; Downloads: 325
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3. Consensus molecular subtypes (CMS) in metastatic colorectal cancer : personalized medicine decisionMartina Reberšek, 2020, review article Abstract: Colorectal cancer (CRC) is one of the most common types of cancer in the world. Metastatic disease is still incurable in most of these patients, but the survival rate has improved by treatment with novel systemic chemotherapy and targeted therapy in combination with surgery. New knowledge of its complex heterogeneity in terms of genetics, epigenetics, transcriptomics and microenvironment, including prognostic and clinical characteristics, led to its classification into various molecular subtypes of metastatic CRC, called consensus molecular subtypes (CMS). The CMS classification thus enables the medical oncologists to adjust the treatment from case to case. They can determine which type of systemic chemotherapy or targeted therapy is best suited to a specific patient, what dosages are needed and in what order. Conclusions. CMS in metastatic CRC are the new tool to include the knowledge of molecular factors, tumour stroma and signalling pathways for personalized, patient-orientated systemic treatment in precision medicine.
Keywords: metastatic colorectal cancer, heterogeneity, biomarkers, consensus molecular subtype
Published in DiRROS: 12.07.2024; Views: 680; Downloads: 141
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4. The coastal ichthyofauna of the Mediterranean coral reef : the case of Mljet National Park (Croatia, southern Adriatic Sea)Lovrenc Lipej, Danijel Ivajnšič, Valentina Pitacco, Borut Mavrič, Domen Trkov, Petar Kružić, 2024, original scientific article Abstract: The authors studied the structure of the coastal fish assemblage in a temperate coral reef within a marine protected area in order to provide a baseline information on the occurrence and temporal distribution of fish and to highlight the importance of the coral reef to ichthyofauna. The coastal fish assemblage was investigated at two sites in Veliko jezero (Mljet National Park) in the southern Adriatic Sea with a non-destructive SCUBA visual technique in the period from 2013 to 2021. Altogether, 38 fish taxa were recorded on the right bank (coral reef) and 36 species on the left bank. The presence of the coral reef at a depth range between 9 m to 12 m is the main factor differentiating the fish fauna in these two areas, which are otherwise governed by the same environmental factors. At the coral reef a decrease in fish diversity was discovered with a steady regression from 2013 to 2021.
Keywords: fish fauna, spatial heterogeneity, Mediterranean coral reef, Cladocora caespitosa, marine protected area, Veliko jezero
Published in DiRROS: 10.05.2024; Views: 610; Downloads: 465
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