E2F1 mediates competition, proliferation and response to cisplatin in cohabitating resistant and sensitive ovarian cancer cells DOI Creative Commons
Andres Felipe Valdivia, Matthew Cowan, Horacio Cárdenas

et al.

Frontiers in Oncology, Journal Year: 2024, Volume and Issue: 14

Published: Jan. 26, 2024

Background Tumor heterogeneity is one of the key factors leading to chemo-resistance relapse. It remains unknown how resistant cancer cells influence sensitive during cohabitation and growth within a heterogenous tumors. The goal our study was identify driving that mediate interactions between determine effects on both phenotypes. Methods We used isogenic ovarian (OC) cell lines pairs, platinum: OVCAR5 vs. CisR PE01 PE04, respectively, perform long term direct culture phenotypical changes interaction these cells. Results Long co-culture OC promoted proliferation (p < 0.001) increased proportion in G1 S cycle phase Direct led decrease IC50 platinum cisplatin-sensitive (5.92 µM 2.79 for PE01, from 2.05 1.51 OVCAR5). RNAseq analysis co-cultured showed enrichment Cell Cycle Control, Cyclins Regulation pathways. transcription factor E2F1 predicted as main effector responsible transcriptomic Western blot qRT-PCR confirmed upregulation vs monoculture. Furthermore, an inhibitor reverted increase rate induced by baseline levels. Conclusion Our data suggest chemo-sensitive -resistant drive higher proliferative state, more responsive platinum. results reveal unexpected effect caused with different rates levels resistance, modelling competition heterogeneous

Language: Английский

Mitochondrial transfer in tunneling nanotubes—a new target for cancer therapy DOI Creative Commons

Fan Guan,

Xiaomin Wu,

Jiatong Zhou

et al.

Journal of Experimental & Clinical Cancer Research, Journal Year: 2024, Volume and Issue: 43(1)

Published: May 21, 2024

A century ago, the Warburg effect was first proposed, revealing that cancer cells predominantly rely on glycolysis during process of tumorigenesis, even in presence abundant oxygen, shifting main pathway energy metabolism from tricarboxylic acid cycle to aerobic glycolysis. Recent studies have unveiled dynamic transfer mitochondria within tumor microenvironment, not only between but also and stromal cells, immune others. In this review, we explore pathways mechanisms mitochondrial as well how these activities promote aggressiveness, chemotherapy resistance, evasion. Further, discuss research progress potential clinical significance targeting phenomena. We highlight therapeutic intercellular a future anti-cancer strategy enhancing cell-mediated immunotherapy.

Language: Английский

Citations

15
The evolutionary theory of cancer: challenges and potential solutions DOI
Lucie Laplane, Carlo C. Maley

Nature reviews. Cancer, Journal Year: 2024, Volume and Issue: 24(10), P. 718 - 733

Published: Sept. 10, 2024

Language: Английский

Citations

13
Betulinic Acid for Glioblastoma Treatment: Reality, Challenges and Perspectives DOI Open Access
Sílvia Fernandes, Mariana Vieira, Cristina Prudêncio

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2108 - 2108

Published: Feb. 9, 2024

Betulinic acid is a naturally occurring compound that can be obtained through methanolic or ethanolic extraction from plant sources, as well chemical synthesis microbial biotransformation. has been investigated for its potential therapeutic properties, and exhibits anti-inflammatory, antiviral, antimalarial, antioxidant activities. Notably, ability to cross the blood-brain barrier addresses significant challenge in treating neurological pathologies. This review aims compile information about impact of betulinic an antitumor agent, particularly context glioblastoma. Importantly, demonstrates selective activity against glioblastoma cells by inhibiting proliferation inducing apoptosis, consistent with observations other cancer types. Compelling evidence published highlights acid's action suppressing Akt/NFκB-p65 signaling cascade enhancing cytotoxic effects chemotherapeutic agent temozolomide. Interesting findings also suggest focus on researching reduction glioblastoma's invasiveness aggressiveness profile. involves modulation extracellular matrix components, remodeling cytoskeleton, secretion proteolytic proteins. Drawing comprehensive review, we conclude formulations nanoparticles and/or ionic liquids are promising drug delivery approaches translation into clinical applications treatment management

Language: Английский

Citations

11
The Therapeutic Mechanisms of Mesenchymal Stem Cells in MS—A Review Focusing on Neuroprotective Properties DOI Open Access
Sonia Gavasso, Torbjørn Kråkenes,

Håkon Olsen

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1365 - 1365

Published: Jan. 23, 2024

In multiple sclerosis (MS), there is a great need for treatment with the ability to suppress compartmentalized inflammation within central nervous system (CNS) and promote remyelination regeneration. Mesenchymal stem cells (MSCs) represent promising therapeutic option, as they have been shown migrate site of CNS injury exert neuroprotective properties, including immunomodulation, neurotrophic factor secretion, endogenous neural cell stimulation. This review summarizes current understanding underlying mechanisms discusses translation MSC transplantation their derivatives from pre-clinical demyelinating models clinical trials MS patients.

Language: Английский

Citations

10
Exercise-induced extracellular vesicles in reprogramming energy metabolism in cancer DOI Creative Commons
Marju Puurand,

Alicia Llorente,

Aija Linē

et al.

Frontiers in Oncology, Journal Year: 2025, Volume and Issue: 14

Published: Jan. 6, 2025

Cancer is caused by complex interactions between genetic, environmental, and lifestyle factors, making prevention strategies, including exercise, a promising avenue for intervention. Physical activity associated with reduced cancer incidence progression systemic anti-cancer effects, improved tumor suppression prolonged survival in preclinical models. Exercise impacts the body's nutrient balance stimulates release of several exercise-induced factors into circulation. The mechanisms how exercise modulates energy metabolism microenvironment through effects mediated, part, extracellular vesicles (EVs) are still unknown. By transferring bioactive cargo such as miRNAs, proteins metabolites, EVs may influence cells altering glycolysis oxidative phosphorylation, potentially shifting metabolic plasticity - hallmark cancer. This short review explores roles mediators to reprogram cellular exchanging information inside microenvironment, influencing immune cells, fibroblast distant cells. Considering this knowledge, further functional studies production pathways could inform more specific interventions enhance therapy improve patient outcomes.

Language: Английский

Citations

1
Exploiting metabolic vulnerability in glioblastoma using a brain-penetrant drug with a safe profile DOI Creative Commons
Audrey Burban,

Cloé Tessier,

Mathieu Larroquette

et al.

EMBO Molecular Medicine, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 3, 2025

Language: Английский

Citations

1
Glioblastoma-Associated Mesenchymal Stem/Stromal Cells and Cancer-Associated Fibroblasts: Partners in Crime? DOI Open Access

Thibault Lootens,

Bart I. Roman, Christian V. Stevens

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(4), P. 2285 - 2285

Published: Feb. 14, 2024

Tumor-associated mesenchymal stem/stromal cells (TA-MSCs) have been recognized as attractive therapeutic targets in several cancer types, due to their ability enhance tumor growth and angiogenesis contribution an immunosuppressive microenvironment (TME). In glioblastoma (GB), stem (MSCs) seem be recruited the site, where they differentiate into glioblastoma-associated (GA-MSCs) under influence of TME. GA-MSCs are reported exert important protumoral functions, such promoting invasion, increasing angiogenesis, stimulating cell (GSC) proliferation stemness, mediating resistance therapy contributing Moreover, could act precursor for cancer-associated fibroblasts (CAFs), which recently identified GB. this review, we provide overview different functions exerted by CAFs current knowledge on relationship between these types. Increasing our understanding interactions signaling pathways relevant models might contribute future regimens targeting GB-associated inhibit render TME less immunosuppressive.

Language: Английский

Citations

7
Metabolic Reprogramming in Glioblastoma Multiforme: A Review of Pathways and Therapeutic Targets DOI Creative Commons

Ashley Irin Cortes Ballen,

Maryam Amosu,

Surya Ravinder

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(18), P. 1574 - 1574

Published: Sept. 19, 2024

Glioblastoma (GBM) is an aggressive and highly malignant primary brain tumor characterized by rapid growth a poor prognosis for patients. Despite advancements in treatment, the median survival time GBM patients remains low. One of crucial challenges understanding treating GBMs involves its remarkable cellular heterogeneity adaptability. Central to proliferation cells their ability undergo metabolic reprogramming. Metabolic reprogramming process that allows cancer alter metabolism meet increased demands survive often oxygen- nutrient-deficient microenvironment. These changes include Warburg effect, alterations several key pathways including glutamine metabolism, fatty acid synthesis, tricarboxylic (TCA) cycle, uptake utilization glutamine, more. complexity adaptability deeper offers hope developing more effective therapeutic interventions against GBMs.

Language: Английский

Citations

6
Endothelial Mitochondria Transfer to Melanoma Induces M2-Type Macrophage Polarization and Promotes Tumor Growth by the Nrf2/HO-1-Mediated Pathway DOI Open Access
Fu‐Chen Kuo, Hsin‐Yi Tsai,

Bi-Ling Cheng

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(3), P. 1857 - 1857

Published: Feb. 3, 2024

Gynecologic tract melanoma is a malignant tumor with poor prognosis. Because of the low survival rate and lack standard treatment protocol related to this condition, investigation mechanisms underlying progression crucial achieve advancements in relevant gynecological surgery treatment. Mitochondrial transfer between adjacent cells microenvironment regulates progression. This study investigated effects endothelial mitochondria on growth activation specific signal transduction pathways following mitochondrial transplantation. Mitochondria were isolated from (ECs) transplanted into B16F10 cells, resulting upregulation proteins associated growth. Furthermore, enhanced antioxidation homeostasis mediated by Sirt1-PGC-1α-Nrf2-HO-1 pathway observed, along inhibition apoptotic protein caspase-3. Finally, transplantation promoted increased M2-type macrophages through Nrf2/HO-1-mediated xenograft animal model. In summary, introduction exogenous ECs growth, indicating role stromal modulating tumor's phenotype. These results provide valuable insights potential targets for

Language: Английский

Citations

4
Diversity of Intercellular Communication Modes: A Cancer Biology Perspective DOI Creative Commons

Thanzeela Ebrahim,

Abdul Shukkur Ebrahim, Mustapha Kandouz

et al.

Cells, Journal Year: 2024, Volume and Issue: 13(6), P. 495 - 495

Published: March 12, 2024

From the moment a cell is on path to malignant transformation, its interaction with other cells from microenvironment becomes altered. The flow of molecular information at heart cellular and systemic fate in tumors, various processes participate conveying key or certain cancer cells. For instance, loss tight junction molecules part signal sent so that they are no longer bound primary tumors thus free travel metastasize. Upon targeting single by therapeutic drug, gap junctions able communicate death by-standing discovery importance novel modes cell–cell communication such as different types extracellular vesicles tunneling nanotubes changing way scientists look these processes. However, all actively involved contexts same time recruited fulfill specific tasks? What does multiplicity mean for overall progression disease? Here, we extend an open invitation think about significance questions, rather than engage elusive attempt systematic repertory mechanisms play.

Language: Английский

Citations

4