Fibroblasts as Turned Agents in Cancer Progression

Abstract

Differentiated epithelial cells reside in the homeostatic microenvironment of the native organ stroma. The stroma supports their normal function, their G0 differentiated state, and their expansion/contraction through the various stages of the life cycle and physiologic functions of the host. When malignant transformation begins, the microenvironment tries to suppress and eliminate the transformed cells, while cancer cells, in turn, try to resist these suppressive efforts. The tumor microenvironment encompasses a large variety of cell types recruited by the tumor to perform different functions, among which fibroblasts are the most abundant. The dynamics of the mutual relationship change as the sides undertake an epic battle for control of the other. In the process, the cancer “wounds” the microenvironment through a variety of mechanisms and attracts distant mesenchymal stem cells to change their function from one attempting to suppress the cancer, to one that supports its growth, survival, and metastasis. Analogous reciprocal interactions occur as well between disseminated cancer cells and the metastatic microenvironment, where the microenvironment attempts to eliminate cancer cells or suppress their proliferation. However, the altered microenvironmental cells acquire novel characteristics that support malignant progression. Investigations have attempted to use these traits as targets of novel therapeutic approaches.

Exploring the multifaceted role of direct interaction between cancer cells and fibroblasts in cancer progression

“…CAFs can also originate from various sources including normal fibroblasts, epithelial cells, endothelial cells, bone marrow-derived mesenchymal stem cells (MSCs), hematopoietic stem cells, cancer stem cells (CSCs), adipocytes, pericytes, and stellate cells ( Kobayashi et al, 2019 ; Ping et al, 2021 ; Kotsiliti, 2022 ; Wieder, 2023 ) via several processes such as activation, recruitment, differentiation, and transdifferentiation ( Ansardamavandi and Tafazzoli-Shadpour, 2021 ; Chhabra and Weeraratna, 2023 ). This diversity in origin also contributes to the heterogeneity of CAFs ( Ping et al, 2021 ; Chhabra and Weeraratna, 2023 ).…”

“…Previous reviews have extensively covered mechanisms of CAFs activation and indirect regulation of tumor cells as well as the heterogeneity of the CAFs phenotypes in individual cancers ( Eble and Niland, 2019 ; Fiori et al, 2019 ; Barrett and Puré, 2020 ; Biffi and Tuveson, 2021 ; Chhabra and Weeraratna, 2023 ; Wieder, 2023 ). In this review, we focus on the specific role of direct contact between CAFs and cancer cells in cancer progression.…”

Dual effects of radiotherapy on tumor microenvironment and its contribution towards the development of resistance to immunotherapy in gastrointestinal and thoracic cancers

“…CAFs are represented by highly heterogeneous cell populations which account for about 50% of the total number of all TME cells ( Butti et al, 2023 ; Wieder, 2023 ). Therefore, CAFs are often defined as stromal TME cells ( De et al, 2021 ; Kochetkova and Samuel, 2021 ; Mor et al, 2022 ).…”

Insights on the Role of Polyphenols in Combating Cancer Drug Resistance

“…In light of these hallmarks of cancer cells, the disease is increasingly thought of as an interchangeable process involving metabolic abnormalities and genetic mutability. Metabolic problems associated with genomic instability are commonly preceded by hypoxia and mitochondrial malfunction, which have been linked to cancer and resistance [ 179 , 180 ]. If left untreated, this issue can progress to the point of somatic genomic instability, which in turn can cause additional mitochondrial abnormalities and metabolic rigidity in tumor cells [ 181 , 182 ].…”