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

Unraveling UPR-Mediated Intercellular Crosstalk: Implications for Immunotherapy Resistance Mechanisms DOI
Lu Si, Qimin Zhou, Rongjie Zhao

et al.

Cancer Letters, Journal Year: 2025, Volume and Issue: unknown, P. 217613 - 217613

Published: March 1, 2025

Language: Английский

Citations

2
Cancer associated fibroblasts and metabolic reprogramming: unraveling the intricate crosstalk in tumor evolution DOI Creative Commons
Fusheng Zhang, Yongsu Ma, Dongqi Li

et al.

Journal of Hematology & Oncology, Journal Year: 2024, Volume and Issue: 17(1)

Published: Sept. 2, 2024

Metabolic reprogramming provides tumors with an energy source and biofuel to support their survival in the malignant microenvironment. Extensive research into intrinsic oncogenic mechanisms of tumor microenvironment (TME) has established that cancer-associated fibroblast (CAFs) metabolic regulates progression through numerous biological activities, including immunosuppression, chronic inflammation, ecological niche remodeling. Specifically, immunosuppressive TME formation is promoted mediators released via CAFs multiple immune cells collectively thereby inducing pre-metastatic formation, ultimately driving a vicious cycle proliferation metastasis. This review comprehensively explores process regulation dynamic evolution tumor-adapted TME, particular focus on by which promote Existing findings confirm components act cooperatively accelerate events. The potential applications challenges targeted therapies based clinical setting are further discussed context advancing related CAFs.

Language: Английский

Citations

14
Secretome of Stromal Cancer-Associated Fibroblasts (CAFs): Relevance in Cancer DOI Creative Commons
Deepshikha Mishra, Debabrata Banerjee

Cells, Journal Year: 2023, Volume and Issue: 12(4), P. 628 - 628

Published: Feb. 15, 2023

The cancer secretome reflects the assortment of proteins released by cells. Investigating cell secretomes not only provides a deeper knowledge healthy and transformed state but also helps in discovery novel biomarkers. Secretomes cells have been studied past, however, contribution stromal needs to be studied. Cancer-associated fibroblasts (CAFs) are one predominantly present populations tumor microenvironment (TME). CAFs play key role functions associated with matrix deposition remodeling, reciprocal exchange nutrients, molecular interactions signaling neighboring TME. or CAFs-secreted factors would help identifying CAF-specific biomarkers, unique druggable targets, an improved understanding for personalized diagnosis prognosis. In this review, we tried include all studies available PubMed keywords "CAFs Secretome". We aim provide comprehensive summary investigating CAF on development, progression, therapeutic outcome. However, challenges process addressed later sections. highlighted clinical relevance analysis CAF-rich types. This review specifically discusses cancers. A components their will identification biomarkers more precise treatment plan.

Language: Английский

Citations

19
Determinants of resistance and response to melanoma therapy DOI

Bailey M. Robertson,

Mitchell E. Fane, Ashani T. Weeraratna

et al.

Nature Cancer, Journal Year: 2024, Volume and Issue: 5(7), P. 964 - 982

Published: July 17, 2024

Language: Английский

Citations

8
FTO elicits tumor neovascularization in cancer-associated fibroblasts through eliminating m6A modifications of multiple pro-angiogenic factors DOI

Qili Liao,

Hanhan Shi, Jie Yang

et al.

Cancer Letters, Journal Year: 2024, Volume and Issue: 592, P. 216911 - 216911

Published: April 27, 2024

Language: Английский

Citations

6
Drug resistance and tumor immune microenvironment: An overview of current understandings (Review) DOI Creative Commons
Yan Liu, Jun Liang, Yanping Zhang

et al.

International Journal of Oncology, Journal Year: 2024, Volume and Issue: 65(4)

Published: Aug. 30, 2024

The use of antitumor drugs represents a reliable strategy for cancer therapy. Unfortunately, drug resistance has become increasingly common and contributes to tumor metastasis local recurrence. immune microenvironment (TME) consists cells, cytokines immunomodulators, collectively they influence the response treatment. Epigenetic changes including DNA methylation histone modification, as well increased exportation have been reported contribute development in cancers. In past few years, majority studies on tumors only focused progression from mechanistic standpoint; examined whether TME can also affect growth resistance. Recently, emerging evidence raised more concerns regarding role present review, it was discussed how suppressive adapts characterized by cooperation cytokines, stromal cells extracellular matrix. Furthermore, reviewed these immunological or metabolic alter immuno‑surveillance thus facilitate addition, potential targets developing novel therapeutic strategies improve individualized therapy treatment were revealed.

Language: Английский

Citations

6
Role and mechanism of fibroblast-activated protein-α expression on the surface of fibroblast-like synoviocytes in rheumatoid arthritis DOI Creative Commons
Zihan Wang, Jinping Wang,

Tianyi Lan

et al.

Frontiers in Immunology, Journal Year: 2023, Volume and Issue: 14

Published: March 17, 2023

Fibroblast-activated protein-α (FAP) is a type II integrated serine protease expressed by activated fibroblasts during fibrosis or inflammation. Fibroblast-like synoviocytes (FLSs) in rheumatoid arthritis (RA) synovial sites abundantly and stably overexpress FAP play important roles regulating the cellular immune, inflammatory, invasion, migration, proliferation, angiogenesis responses region. Overexpression of regulated initial inflammatory microenvironment disease epigenetic signaling, which promotes RA development FLSs affecting signaling cross-linking with other cells at local synovium stimulation. At present, several treatment options targeting are process development. This review discusses basic features on surface its role pathophysiology advances targeted therapies.

Language: Английский

Citations

13
The Clinical Significance and Involvement in Molecular Cancer Processes of Chemokine CXCL1 in Selected Tumors DOI Open Access
Jan Korbecki, Mateusz Bosiacki, Iwona Szatkowska

et al.

International Journal of Molecular Sciences, Journal Year: 2024, Volume and Issue: 25(8), P. 4365 - 4365

Published: April 15, 2024

Chemokines play a key role in cancer processes, with CXCL1 being well-studied example. Due to the lack of complete summary CXCL1’s literature, this study, we examine significance various cancers such as bladder, glioblastoma, hemangioendothelioma, leukemias, Kaposi’s sarcoma, lung, osteosarcoma, renal, and skin (malignant melanoma, basal cell carcinoma, squamous carcinoma), along thyroid cancer. We focus on understanding how is involved processes these specific types tumors. look at affects cells, including their proliferation, migration, EMT, metastasis. also explore influences other cells connected tumors, like promoting angiogenesis, recruiting neutrophils, affecting immune functions. Additionally, discuss clinical aspects by exploring levels relate staging, lymph node metastasis, patient outcomes, chemoresistance, radioresistance.

Language: Английский

Citations

5
Melanoma cells induce dedifferentiation and metabolic changes in adipocytes present in the tumor niche DOI Creative Commons
Aleksandra Simiczyjew, Justyna Wądzyńska, Katarzyna Pietraszek‐Gremplewicz

et al.

Cellular & Molecular Biology Letters, Journal Year: 2023, Volume and Issue: 28(1)

Published: July 22, 2023

Abstract Background One of the factors that affect progression melanoma is tumor microenvironment, which consists cellular elements, extracellular matrix, acidification, and a hypoxic state. Adipocytes are one types cell present in niche localized deepest layer skin. However, relationship between fat cells remains unclear. Methods We assessed influence on adipocytes using an indirect coculture system. estimated level cancer-associated adipocyte (CAA) markers through quantitative PCR analysis. The fibroblastic phenotype CAAs was confirmed by staining western blotting lipid content detection LipidSpot analysis Oil Red O. expression proteins involved synthesis, delipidation, metabolic processes were or Lactate secretion established Lactate-Glo™ assay. Proteins secreted identified cytokine angiogenesis arrays. proliferation cocultured with XTT Statistical performed one-way ANOVA followed Tukey’s test GraphPad Prism 7 software. Results Obtained decreased levels leptin, adiponectin, resistin, FABP4. presented features, such as similar proteolytic pattern to 3T3L1 fibroblasts increased vimentin TGFβRIII. Melanoma led reduction CAAs, possibly downregulation synthesis pathways (lower FADS, SC4MOL, FASN) enhancement lipolysis (higher phosphorylation ERK STAT3). higher IL6 SerpinE1 produced less CCL2, CXCL1, angiogenic molecules. also showed changes comprising lactate enhanced production glucose, lactate, ion transporters. In addition, observed following resulted rate cancer cells. Conclusions adipocytes, might be related delipidation synthesis. Fibroblast-like may reason for accelerated

Language: Английский

Citations

11
The tumor immune microenvironment in primary cutaneous melanoma DOI Creative Commons
Catherine Zilberg, Angela L. Ferguson, J. Guy Lyons

et al.

Archives of Dermatological Research, Journal Year: 2025, Volume and Issue: 317(1)

Published: Jan. 18, 2025

Abstract Melanoma is an immunogenic tumor. The melanoma tumor immune microenvironment (TIME) made up of a heterogenous mix both and non-immune cells as well multitude signaling molecules. interactions between cells, molecules affect progression therapeutic responses. Understanding the composition function TIME in primary cutaneous useful for prognostication decisions. This review provides overview components melanoma, their influence on clinical outcomes.

Language: Английский

Citations

0