The impact of cellular elements of TME on melanoma biology and its sensitivity to EGFR and MET targeted therapy DOI Creative Commons
Justyna Wądzyńska, Aleksandra Simiczyjew, Katarzyna Pietraszek‐Gremplewicz

et al.

Biochimica et Biophysica Acta (BBA) - Molecular Cell Research, Journal Year: 2023, Volume and Issue: 1870(7), P. 119549 - 119549

Published: July 27, 2023

Microenvironment of the melanoma consists cellular elements like fibroblasts, adipocytes, and keratinocytes as well extracellular matrix physicochemical conditions. In our previous research, we have established that influences strongly above mentioned cells present in tumor niche recruits them to support cancer progression. this work, evaluated impact cancer-associated cells, namely fibroblasts (CAFs), adipocytes (CAAs), (CAKs) on proliferation, signaling pathways activation, metabolism effectiveness used anti-cancer therapy. Obtained results indicated elevated phosphorylation STAT3, upregulated GLUT1 GLUT3 downregulated MCT-1 expression level under influence all examined niche. The proliferation was increased after co-culture with CAFs CAKs, while epithelial-mesenchymal transition markers' raised presence CAAs. perilipin 2 lipid content Moreover, CYP1A1, gene encoding drug metabolizing protein, co-cultured CAKs prompted us verify previously proposed by anti-melanoma therapy based combination EGFR MET inhibitors. indicate designed is still efficient, even if keratinocytes, are vicinity.

Language: Английский

Cross‐Talk Signaling Between Non‐Small Cell Lung Cancer Cell Lines and Fibroblasts Attenuates the Cytotoxic Effect of Cisplatin DOI Open Access
Nouran Ebid, Marwa Sharaky, Abeer Elkhoely

et al.

Journal of Biochemical and Molecular Toxicology, Journal Year: 2025, Volume and Issue: 39(3)

Published: March 1, 2025

ABSTRACT Fibroblasts represent one of the most crucial cell types in tumor microenvironment (TME), playing a major role chemoresistance development. This study investigated ability fibroblasts to alter response non‐small lung cancer (NSCLC) lines cisplatin exposure. A cytotoxicity assay was performed determine IC 50 using MTT. The on NSCLC A549 and H1299 monocultures co‐cultures with fibroblasts. co‐culture directly HSF line indirectly through conditioned media. ELISA technique then used expression biochemical markers at various time points before after We observed time‐dependent evolution fibroblast‐cancer interplay. Initially, fibroblast enhanced cytotoxic effect cisplatin, as reflected by decreased values 24 h co‐culture. However, prolonged durations (48–96 h) led emergence resistance, coinciding increased altered key markers. findings suggest that undergo potential identity switch over time, transitioning from tumor‐restrictive tumor‐promoting phenotype. associated activation EGFR FGF signaling pathways, angiogenic metastasis (e.g., VEGF, MMP2 & MMP9), inhibition apoptosis reduced caspase expression). Our results may initially potentiate cells; however, manner, attenuates efficacy cisplatin.

Language: Английский

Citations

0
The Dynamic Interplay between Melanoma Cells and CAFs: Implications Drug Resistance and Immune Evasion and Possible Therapeutics DOI
Chou‐Yi Hsu, Raed Obaid Saleh, Mohammed Sani Jaafaru

et al.

Experimental Cell Research, Journal Year: 2025, Volume and Issue: unknown, P. 114581 - 114581

Published: April 1, 2025

Language: Английский

Citations

0
The Cross Talk between Cellular Senescence and Melanoma: From Molecular Pathogenesis to Target Therapies DOI Open Access
Jiahua Liu, Runzi Zheng, Yanghuan Zhang

et al.

Cancers, Journal Year: 2023, Volume and Issue: 15(9), P. 2640 - 2640

Published: May 6, 2023

Melanoma is a malignant skin tumor that originates from melanocytes. The pathogenesis of melanoma involves complex interaction occurs between environmental factors, ultraviolet (UV)-light damage, and genetic alterations. UV light the primary driver aging process development melanoma, which can induce reactive oxygen species (ROS) production presence DNA damage in cells, results cell senescence. As cellular senescence plays an important role relationship exists present study provides insight into literature concerning topic at discusses including mechanisms drive progression, microenvironment relation to therapeutics melanoma. This review focuses on defining carcinogenesis targeting senescent cells through therapeutic approaches, highlighting areas require more extensive research field.

Language: Английский

Citations

10
Quantifying in vivo collagen reorganization during immunotherapy in murine melanoma with second harmonic generation imaging DOI
Alexa R. Heaton,

Nathaniel J. Burkard,

Paul M. Sondel

et al.

Biophotonics discovery., Journal Year: 2024, Volume and Issue: 1(01)

Published: May 20, 2024

Increased collagen linearization and deposition during tumorigenesis can impede immune cell infiltration lead to tumor metastasis. Although melanoma is well studied in immunotherapy research, studies that quantify changes progression treatment are lacking.

Language: Английский

Citations

3
Extracellular vesicles derived from melanoma cells induce carcinoma‐associated fibroblasts via miR‐92b‐3p mediated downregulation of PTEN DOI Creative Commons

Stefanie Kewitz‐Hempel,

Nicola Windisch,

Gerd Hause

et al.

Journal of Extracellular Vesicles, Journal Year: 2024, Volume and Issue: 13(9)

Published: Sept. 1, 2024

Abstract In melanoma, carcinoma‐associated fibroblasts (CAFs) are important cellular components in the tumour microenvironment due to their potential promote growth and metastatic spread of malignant cells. Melanoma cells have ability affect non‐tumour by releasing extracellular vesicles (EVs). The mechanisms responsible for reprogramming normal dermal (NHDFs) into CAFs remain incompletely understood. However, it is likely thought be mediated melanoma‐specific miRNAs, which transported EVs derived from melanoma Therefore, we wondered if one most enriched miRNAs secreted cells, miR‐92b‐3p, involved conversion CAFs. We observed that cell‐derived indeed delivered miR‐92b‐3p NHDFs its accumulation correlated with CAF formation, as demonstrated enhanced expression marker genes increased proliferation migration. Overexpression revealed similar results, while deficient did not induce a phenotype. As target identified PTEN, whose repression led markers. thus provide novel pathway intercellular communication control transformation virtue EV‐transported miRNAs.

Language: Английский

Citations

3
The Impact of Iron on Cancer-Related Immune Functions in Oncology: Molecular Mechanisms and Clinical Evidence DOI Open Access
Omar Badran, Idan Cohen, Gil Bar‐Sela

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(24), P. 4156 - 4156

Published: Dec. 13, 2024

Iron metabolism plays a dual role in cancer, serving as an essential nutrient for cellular functions and potential catalyst tumor growth immune evasion. Here, we cover the complex interplay between iron levels within serum or microenvironment cancer therapy, focusing on how deficiency overload can impact function, progression, treatment efficacy. On one hand, highlight factor of primary responses its adverse effects anti-cancer immunotherapy other also stress contributing to growth, creating suppressive that hinders checkpoint inhibitor immunotherapy. Overall, emphasize necessity personalized management oncology patients critical element optimization achieve favorable outcomes. Based these considerations, believe close careful monitoring tailored balancing supplementation strategies should be subject further clinical studies, routine implemented practice integrated into therapy protocols.

Language: Английский

Citations

3
Tumor Metabolic Heterogeneity DOI
Marina V. Shirmanova, Snezhana D Sinyushkina, A. D. Komarova

et al.

Молекулярная биология, Journal Year: 2023, Volume and Issue: 57(6), P. 1130 - 1149

Published: Nov. 1, 2023

Currently, much attention in oncology is devoted to the issues of tumor heterogeneity, which creates serious problems diagnosis and therapy malignant neoplasms. Intertumoral intratumoral differences relate various characteristics aspects vital activity cells, including cellular metabolism. This review provides general information about metabolic heterogeneity with a focus on energy metabolism, its causes, mechanisms research methods. Among methods, fluorescence lifetime imaging described more detail as new promising method for observing at level. The demonstrates importance studying features metabolism identifying intra- intertumoral differences.

Language: Английский

Citations

9
Nano-adjuvants and immune agonists promote antitumor immunity of peptide amphiphiles DOI
Huan Yan,

Guibin Lin,

Zhanyan Liu

et al.

Acta Biomaterialia, Journal Year: 2023, Volume and Issue: 161, P. 213 - 225

Published: March 10, 2023

Language: Английский

Citations

8
Unveiling the Dynamic Interplay between Cancer Stem Cells and the Tumor Microenvironment in Melanoma: Implications for Novel Therapeutic Strategies DOI Open Access
Patrízia Limonta, Raffaella Chiaramonte, Lavinia Casati

et al.

Cancers, Journal Year: 2024, Volume and Issue: 16(16), P. 2861 - 2861

Published: Aug. 16, 2024

Cutaneous melanoma still represents a significant health burden worldwide, being responsible for the majority of skin cancer deaths. Key advances in therapeutic strategies have significantly improved patient outcomes; however, most patients experience drug resistance and tumor relapse. Cancer stem cells (CSCs) are small subpopulation different tumors, including melanoma, endowed with distinctive capacities self-renewal differentiation into bulk cells. Melanoma CSCs characterized by expression specific biomarkers intracellular pathways; moreover, they play pivotal role onset, progression resistance. In recent years, great efforts been made to dissect molecular mechanisms underlying protumor activities provide basis novel CSC-targeted therapies. Herein, we highlight intricate crosstalk between bystander microenvironment (TME), immune cells, endothelial cancer-associated fibroblasts (CAFs), its progression. Specifically, discuss peculiar escape host surveillance, recruit immunosuppressive educate toward an phenotype. We also address currently investigated that could pave way new promising approaches care.

Language: Английский

Citations

2
Melanoma stimulates the proteolytic activity of HaCaT keratinocytes DOI Creative Commons

Justyna Mazurkiewicz,

Aleksandra Simiczyjew, Ewelina Dratkiewicz

et al.

Cell Communication and Signaling, Journal Year: 2022, Volume and Issue: 20(1)

Published: Sept. 19, 2022

Abstract Background Keratinocytes constitute a major part of the melanoma microenvironment, considering their protective role towards melanocytes in physiological conditions. However, interactions with tumor cells following melanomagenesis are still unclear. Methods We used two vitro models (melanoma-conditioned media and indirect co-culture keratinocytes on Transwell inserts) to activate immortalized cancer-associated ones. Western Blotting qPCR were evaluate keratinocyte markers mediators cell invasiveness protein mRNA expression level respectively. The levels activity proteases cytokines analysed using gelatin-FITC staining, gelatin zymography, chemiluminescent enzymatic test, as well arrays. Finally, further study functional changes influenced by we assessed rate proliferation invasive abilities employing wound healing assay filter invasion method. Results HaCaT activated through incubation melanoma-conditioned medium or exhibit properties less differentiated (downregulation cytokeratin 10), which also prefer form connections cancer rather than adjacent (decreased E-cadherin). While they express only small number cytokines, variety secreted is quite prominent especially that several them never reported secretome keratinocytes’ (e.g., matrix metalloproteinase 3 (MMP3), ADAM metallopeptidase thrombospondin type 1 motif 1). Activated seem high proteolytic mediated MMP9 MMP14, reduced TIMPs (tissue inhibitor metalloproteinases), upregulation ERK increased MMP regulators-RUNX2 galectin 3. Moreover, show slightly elevated migratory abilities, however inserts. Conclusions Our offers more in-depth view residing niche, drawing attention unique factors could be support surrounding tissues.

Language: Английский

Citations

11