Contribution of Tumor Microenvironment (TME) to Tumor Apoptosis, Angiogenesis, Metastasis, and Drug Resistance

Overview

Journal Med Oncol

Publisher Springer

Specialty Oncology

Date 2025 Mar 15

PMID 40087196

Authors

Yanhong Xiao

Mahan Hassani

Melina Barahouei Moghaddam

Ahmad Fazilat

Masoud Ojarudi

Mohammad Valilo

Affiliations

Soon will be listed here.

Abstract

The tumor microenvironment (TME) contains tumor cells, surrounding cells, and secreted factors. It provides a favorable environment for the maintenance of cancer stem cells (CSCs), the spread of cancer cells to metastatic sites, angiogenesis, and apoptosis, as well as the growth, proliferation, invasion, and drug resistance of cancer cells. Cancer cells rely on the activation of oncogenes, inactivation of tumor suppressors, and the support of a normal stroma for their growth, proliferation, and survival, all of which are provided by the TME. The TME is characterized by the presence of various cells, including cancer-associated fibroblasts (CAFs), tumor-associated macrophages (TAMs), CD8 + cytotoxic T cells (CTLs), regulatory T cells (Tregs), myeloid-derived suppressor cells (MDSCs), mesenchymal stem cells (MSCs), endothelial cells, adipocytes, and neuroendocrine (NE) cells. The high expression of inflammatory cytokines, angiogenic factors, and anti-apoptotic factors, as well as drug resistance mechanisms in the TME, contributes to the poor therapeutic efficacy of anticancer drugs and tumor progression. Hence, this review describes the mechanisms through which the TME is involved in apoptosis, angiogenesis, metastasis, and drug resistance in tumor cells.

References

Siegel R, Giaquinto A, Jemal A . Cancer statistics, 2024. CA Cancer J Clin. 2024; 74(1):12-49. DOI: 10.3322/caac.21820. View

Bizuayehu H, Ahmed K, Kibret G, Dadi A, Belachew S, Bagade T . Global Disparities of Cancer and Its Projected Burden in 2050. JAMA Netw Open. 2024; 7(11):e2443198. PMC: 11539015. DOI: 10.1001/jamanetworkopen.2024.43198. View

Sadeghi Rad H, Monkman J, Warkiani M, Ladwa R, OByrne K, Rezaei N . Understanding the tumor microenvironment for effective immunotherapy. Med Res Rev. 2020; 41(3):1474-1498. PMC: 8247330. DOI: 10.1002/med.21765. View

Frisch J, Angenendt A, Hoth M, Roma L, Lis A . STIM-Orai Channels and Reactive Oxygen Species in the Tumor Microenvironment. Cancers (Basel). 2019; 11(4). PMC: 6520831. DOI: 10.3390/cancers11040457. View

Hanahan D, Coussens L . Accessories to the crime: functions of cells recruited to the tumor microenvironment. Cancer Cell. 2012; 21(3):309-22. DOI: 10.1016/j.ccr.2012.02.022. View

Ni Y, Zhou X, Yang J, Shi H, Li H, Zhao X . The Role of Tumor-Stroma Interactions in Drug Resistance Within Tumor Microenvironment. Front Cell Dev Biol. 2021; 9:637675. PMC: 8173135. DOI: 10.3389/fcell.2021.637675. View

Denisenko T, Budkevich I, Zhivotovsky B . Cell death-based treatment of lung adenocarcinoma. Cell Death Dis. 2018; 9(2):117. PMC: 5833343. DOI: 10.1038/s41419-017-0063-y. View

Balkwill F, Capasso M, Hagemann T . The tumor microenvironment at a glance. J Cell Sci. 2013; 125(Pt 23):5591-6. DOI: 10.1242/jcs.116392. View

de Visser K, Joyce J . The evolving tumor microenvironment: From cancer initiation to metastatic outgrowth. Cancer Cell. 2023; 41(3):374-403. DOI: 10.1016/j.ccell.2023.02.016. View

10.

Arnol D, Schapiro D, Bodenmiller B, Saez-Rodriguez J, Stegle O . Modeling Cell-Cell Interactions from Spatial Molecular Data with Spatial Variance Component Analysis. Cell Rep. 2019; 29(1):202-211.e6. PMC: 6899515. DOI: 10.1016/j.celrep.2019.08.077. View

11.

Armingol E, Officer A, Harismendy O, Lewis N . Deciphering cell-cell interactions and communication from gene expression. Nat Rev Genet. 2020; 22(2):71-88. PMC: 7649713. DOI: 10.1038/s41576-020-00292-x. View

12.

Dominiak A, Chelstowska B, Olejarz W, Nowicka G . Communication in the Cancer Microenvironment as a Target for Therapeutic Interventions. Cancers (Basel). 2020; 12(5). PMC: 7281160. DOI: 10.3390/cancers12051232. View

13.

Dobie C, Skropeta D . Insights into the role of sialylation in cancer progression and metastasis. Br J Cancer. 2020; 124(1):76-90. PMC: 7782833. DOI: 10.1038/s41416-020-01126-7. View

14.

Sharma P, Siddiqui B, Anandhan S, Yadav S, Subudhi S, Gao J . The Next Decade of Immune Checkpoint Therapy. Cancer Discov. 2021; 11(4):838-857. DOI: 10.1158/2159-8290.CD-20-1680. View

15.

van Niel G, Carter D, Clayton A, Lambert D, Raposo G, Vader P . Challenges and directions in studying cell-cell communication by extracellular vesicles. Nat Rev Mol Cell Biol. 2022; 23(5):369-382. DOI: 10.1038/s41580-022-00460-3. View

16.

Lucotti S, Kenific C, Zhang H, Lyden D . Extracellular vesicles and particles impact the systemic landscape of cancer. EMBO J. 2022; 41(18):e109288. PMC: 9475536. DOI: 10.15252/embj.2021109288. View

17.

Choi H, Moon A . Crosstalk between cancer cells and endothelial cells: implications for tumor progression and intervention. Arch Pharm Res. 2018; 41(7):711-724. DOI: 10.1007/s12272-018-1051-1. View

18.

Wei R, Liu S, Zhang S, Min L, Zhu S . Cellular and Extracellular Components in Tumor Microenvironment and Their Application in Early Diagnosis of Cancers. Anal Cell Pathol (Amst). 2020; 2020:6283796. PMC: 7199555. DOI: 10.1155/2020/6283796. View

19.

Wang M, Zhao J, Zhang L, Wei F, Lian Y, Wu Y . Role of tumor microenvironment in tumorigenesis. J Cancer. 2017; 8(5):761-773. PMC: 5381164. DOI: 10.7150/jca.17648. View

20.

Nurmik M, Ullmann P, Rodriguez F, Haan S, Letellier E . In search of definitions: Cancer-associated fibroblasts and their markers. Int J Cancer. 2019; 146(4):895-905. PMC: 6972582. DOI: 10.1002/ijc.32193. View