The role of tumor microenvironment on cancer stem cell fate in solid tumors - Review overview

Sep 24, 2026

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Cancer stem cells (CSCs) are recognized as key drivers of tumor initiation, invasion, metastasis, and resistance to therapies, making them a promising target for cancer treatment. This review explains how CSC-related progression can be shaped by mechanical forces, epithelial-mesenchymal transition, cellular plasticity, and distinct metabolism pathways. It also highlights tumor microenvironment (TME) players and how their signals regulate CSC behavior in solid tumors. The article outlines current understanding and identifies the need for further studies to reveal additional mechanisms.

LanguageEnglish

CategoryResearch & Report

FormatPDF

Pages23

Reading Time58 min

AccessFree to download

Abstract

Introduction

Cancer stem cells and tumor progression

Role of tumor microenvironment in CSC plasticity and metabolism

Review focus and future directions

Razi etal. Cell Communication and Signaling (2023) 21:143 [https://doi.org/10.1186/s12964-023-01129-w](https://doi.org/10.1186/s12964-023-01129-w) Cell Communication and Signaling REVIEW Open Access The role of tumor microenvironment on cancer stem cell fate in solid tumors Sara Razi 1, Amin Haghparast2, Sepide Chodari Khameneh 1, Amin Ebrahimi Sadrabadi3,4, Fatemeh Aziziyan5,6, Maryam Bakhtiyari6,7, Mohsen Nabi‑Afjadi5, Vahideh Tarhriz8*, Arsalan Jalili3,9* and Hamidreza Zalpoor6,10* Abstract In the last few decades, the role of cancer stem cells in initiating tumors, metastasis, invasion, and resistance to therapies has been recognized as a potential target for tumor therapy. Understanding the mechanisms by which CSCs contribute to cancer progression can help to provide novel therapeutic approaches against solid tumors. In this line, the effects of mechanical forces on CSCs such as epithelial‑mesenchymal transition, cellular plasticity, etc., the metabolism pathways of CSCs, players of the tumor microenvironment, and their influence on the regulating of CSCs can lead to cancer progression. This review focused on some of these mechanisms of CSCs, paving the way for abetter understanding of their regulatory mechanisms and developing platforms for targeted therapies. While progress has been made in research, more studies will be required in the future to explore more aspects of how CSCs contrib‑ ute to cancer progression. Keywords Cancer stem cells, Tumor microenvironment, Metabolism, Solid tumors, EMT, Cellular plasticity, Signaling pathways *Correspondence: Vahideh Tarhriz [t.tarhriz@yahoo.com](t.tarhriz@yahoo.com); [tarhrizv@tbzmed.ac.ir](tarhrizv@tbzmed.ac.ir) Arsalan Jalili [Jalili.arsalan@yahoo.com](Jalili.arsalan@yahoo.com)[ ](Jalili.arsalan@yahoo.com)Hamidreza Zalpoor [hamidreza.zlpr1998@gmail.com](hamidreza.zlpr1998@gmail.com) 1 Vira Pioneers of Modern Science (VIPOMS), Tehran, Iran 2 GenomeFan, Tehran, Iran 3 Department of Stem Cells and Developmental Biology, Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACER, Tehran, Iran 4 Cytotech and Bioinformatics Research Group, Tehran, Iran 5 Department of Biochemistry, Faculty of Biological Sciences, Tarbiat Modares University, Tehran, Iran 6 Network of Immunity in Infection, Malignancy & Autoimmunity (NIIMA), Universal Scientific Education & Research Network (USERN), Tehran, Iran 7 Department of Medical Laboratory Sciences, Faculty of Allied Medicine, Qazvin University of Medical Sciences, Qazvin, Iran 8 Infectious and Tropical Diseases Research Center, Tabriz University of Medical Sciences, P. O. Box 5163639888, Tabriz, Iran 9 Parvaz Research Ideas Supporter Institute, Tehran, Iran 10 Shiraz Neuroscience Research Center, Shiraz University of Medical Sciences, Shiraz, Iran Introduction Cancer is still one of the primary reasons of death all around the world with several complications such as metastasis, heterogeneity in cells, invasion, relapse, and therapy resistance [1]. In the last two decades, the discovery of the origin of cancer has led to a better understanding of the mechanism of malignancies. In this line, the model of cancer stem cells (CSCs) has been widely accepted in different malignancies as potential factors in charge of invasion and therapy resistance [2–5]. Despite advances in screening programs and the development of new immunotherapy methods, eradication or representation of a defined method to identify, recognize, and isolate the population of turmeric cells has not yet succeeded and remains unknown. One of the challenges ahead of the eradication of CSCs is reckoned to stem from the plasticity and heterogeneity that these cells show in the microenvironment of a tumor [6]. This plasticity could take root in the metabolism of these cells, which has been introduced to be one of the ways © The Author(s) 2023. Open Access This article is licensed under a Creative Commons Att

FAQs

Why are cancer stem cells considered a potential target in solid tumors?

Cancer stem cells are associated with initiating tumors, invasion, metastasis, and resistance to therapies. Targeting their regulating mechanisms may enable more effective treatments.

What mechanisms does the review link to cancer stem cell fate in solid tumors?

The review highlights mechanical forces affecting CSCs, including epithelial-mesenchymal transition and cellular plasticity, as well as CSC metabolism pathways and tumor microenvironment signaling.

How does the tumor microenvironment influence CSC behavior?

The tumor microenvironment includes factors such as tumor-associated macrophages, cancer-associated fibroblasts, endothelial and immune cells. Their signals and conditions can drive CSC plasticity and metabolism-related regulation.

Sep 24, 2026

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