Fibroblasts in cancer dormancy: foe or friend?

Dai, Li; Li, Mao; Zhang, Wei‐long; Tang, Ya‐Jie; Tang, Yaling; Liang, Xin‐hua

doi:10.1186/s12935-021-01883-2

Cited by 11 publications

(3 citation statements)

References 91 publications

(77 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The role of fibroblasts in the tumor microenvironment is one of the most reviewed topics in cancer biology. Fibroblasts have been called spears and shields [ 14 ], foes and friends [ 431 ], seeds fertilizing the soil [ 432 ], partners-in-crime [ 432 ], cockroaches [ 13 ], maestros orchestrating tissue regeneration [ 54 ], protecting angels and wicked witches [ 433 ], diabolic liaisons [ 434 ], two sides of the same coin, in the case of MSCs and fibroblasts [ 53 ], the dark side of the coin, in the case of CAFs [ 435 ], drivers or passengers, in the case of fibrous stroma [ 436 ], and plying the double-edged sword of fibrosis [ 437 ]. This anthropomorphized turning of the agent or tool, which is the fibroblast guarding the host against the insurgent aspirations of cancer, has implicitly been covered as well by the countless articles on cancer cell fusion with mesenchymal stem cells, exosomes, miRNA transfers, cytokine, chemokine and growth factor secretions, immune cell activations, and other mechanisms.…”

Section: Cancer-associated Fibroblastsmentioning

confidence: 99%

Fibroblasts as Turned Agents in Cancer Progression

Wieder

2023

Cancers

View full text Add to dashboard Cite

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.

show abstract

Section: Cancer-associated Fibroblastsmentioning

confidence: 99%

Fibroblasts as Turned Agents in Cancer Progression

Wieder

2023

Cancers

View full text Add to dashboard Cite

show abstract

“…Cancer-associated fibroblasts (CAFs) may influence cancer dormancy by producing and secreting a collection of different molecules, including TGFβ, interferons, interleukins, chemokines, and other cytokines [79]. In ER-breast cancer, CAF-secreted IFN-β drives a persistent activation of the IFN-β/IFNAR/IRF7 signaling axis in cancer cells, thereby favoring chemotherapy-induced dormancy [80].…”

Section: Extracellular Mechanismsmentioning

confidence: 99%

Metabolic Features of Tumor Dormancy: Possible Therapeutic Strategies

Pranzini

Raugei

Taddei

2022

Cancers

View full text Add to dashboard Cite

Tumor relapse represents one of the main obstacles to cancer treatment. Many patients experience cancer relapse even decades from the primary tumor eradication, developing more aggressive and metastatic disease. This phenomenon is associated with the emergence of dormant cancer cells, characterized by cell cycle arrest and largely insensitive to conventional anti-cancer therapies. These rare and elusive cells may regain proliferative abilities upon the induction of cell-intrinsic and extrinsic factors, thus fueling tumor re-growth and metastasis formation. The molecular mechanisms underlying the maintenance of resistant dormant cells and their awakening are intriguing but, currently, still largely unknown. However, increasing evidence recently underlined a strong dependency of cell cycle progression to metabolic adaptations of cancer cells. Even if dormant cells are frequently characterized by a general metabolic slowdown and an increased ability to cope with oxidative stress, different factors, such as extracellular matrix composition, stromal cells influence, and nutrient availability, may dictate specific changes in dormant cells, finally resulting in tumor relapse. The main topic of this review is deciphering the role of the metabolic pathways involved in tumor cells dormancy to provide new strategies for selectively targeting these cells to prevent fatal recurrence and maximize therapeutic benefit.

show abstract

“…The result showed that these nine genes are primarily highly expressed in fibroblasts (Figures 3E,F). While there is little evidence to show a direct correlation between fibroblasts and cancer dormancy, CAFs are the major subpopulation of fibroblasts in tumor stroma, and CAFs are also related to dormancy-related factors such as transforming growth factor-beta (TGF-β), interferon (IFN), insulin-like growth factor (IGF), fibroblast growth factor (FGF), macrophage-stimulating factor (M-SCF), and interleukin (IL) (Dai et al, 2021). This may indicate that CAFs can influence the state of cancer cells through remodeling the ECM, producing exosomes, mediating the balance of angiogenesis, or recruiting immune cells.…”

Section: Drivers Of Dormant State: Dormancy-related Genes and Synergi...mentioning

confidence: 99%

Transcriptomics and Metabolomics Identify Drug Resistance of Dormant Cell in Colorectal Cancer

Xie

Huang

et al. 2022

Front. Pharmacol.

View full text Add to dashboard Cite

Background: Tumor dormancy is an important way to develop drug resistance. This study aimed to identify the characteristics of colorectal cancer (CRC) cell dormancy.Methods: Based on the CRC cohorts, a total of 1,044 CRC patients were included in this study, and divided into a dormant subgroup and proliferous subgroup. Non-negative matrix factorization (NMF) was used to distinguish the dormant subgroup of CRC via transcriptome data of cancer tissues. Gene Set Enrichment Analysis (GSEA) was used to explore the characteristics of dormant CRC. The characteristics were verified in the cell model, which was used to predict key factors driving CRC dormancy. Potential treatments for CRC dormancy were also examined.Results: The dormant subgroup had a poor prognosis and was more likely to relapse. GSEA analysis showed two defining characteristics of the dormant subgroup, a difference in energy metabolism and synergistic effects of cancer-associated fibroblasts (CAFs), which were verified in a dormant cell model. Transcriptome and clinical data identified LMOD1, MAB21L2, and ASPN as important factors associated with cell dormancy and verified that erlotinib, and CB-839 were potential treatment options.Conclusion: Dormant CRC is associated with high glutamine metabolism and synergizes with CAFs in 5-FU resistance, and the key effectors are LMOD1, MAB21L2, and ASPN. Austocystin D, erlotinib, and CB-839 may be useful for dormant CRC.

show abstract

Fibroblasts in cancer dormancy: foe or friend?

Cited by 11 publications

References 91 publications

Fibroblasts as Turned Agents in Cancer Progression

Fibroblasts as Turned Agents in Cancer Progression

Metabolic Features of Tumor Dormancy: Possible Therapeutic Strategies

Transcriptomics and Metabolomics Identify Drug Resistance of Dormant Cell in Colorectal Cancer

Contact Info

Product

Resources

About