Characterising cancer-associated fibroblast heterogeneity in non-small cell lung cancer: a systematic review and meta-analysis

Irvine, Andrew J; Waise, Sara; Green, Edward W.; Stuart, Beth; Thomas, Gareth J.

doi:10.1038/s41598-021-81796-2

Cited by 32 publications

(38 citation statements)

References 105 publications

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“…A recent seminal Consensus Statement on the basis of a meeting of experts in the field, underlined the degree of specialization among these cells (70). Such a specialization may explain the distinct functional sub-groups of CAFs identified by various markers (71). Our current understanding of these cells include the fact that most markers do not represent the whole CAF population.…”

Section: Heterogeneity Of Cafsmentioning

confidence: 99%

CAFs Interacting With TAMs in Tumor Microenvironment to Enhance Tumorigenesis and Immune Evasion

Günaydın

2021

Front. Oncol.

102

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Cancer associated fibroblasts (CAFs) and tumor associated macrophages (TAMs) are among the most important and abundant players of the tumor microenvironment. CAFs as well as TAMs are known to play pivotal supportive roles in tumor growth and progression. The number of CAF or TAM cells is mostly correlated with poor prognosis. Both CAFs and TAMs are in a reciprocal communication with the tumor cells in the tumor milieu. In addition to such interactions, CAFs and TAMs are also involved in a dynamic and reciprocal interrelationship with each other. Both CAFs and TAMs are capable of altering each other’s functions. Here, the current understanding of the distinct mechanisms about the complex interplay between CAFs and TAMs are summarized. In addition, the consequences of such a mutual relationship especially for tumor progression and tumor immune evasion are highlighted, focusing on the synergistic pleiotropic effects. CAFs and TAMs are crucial components of the tumor microenvironment; thus, they may prove to be potential therapeutic targets. A better understanding of the tri-directional interactions of CAFs, TAMs and cancer cells in terms of tumor progression will pave the way for the identification of novel theranostic cues in order to better target the crucial mechanisms of carcinogenesis.

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Section: Heterogeneity Of Cafsmentioning

confidence: 99%

CAFs Interacting With TAMs in Tumor Microenvironment to Enhance Tumorigenesis and Immune Evasion

Günaydın

2021

Front. Oncol.

102

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“…The vimentin-positive cells in the CXPA tissues were moderately scattered among cancer cells, as well as their surrounding fibrotic regions, and some of them were also positively stained with α-SMA, indicating that cancer-associated fibroblasts (CAFs) were present abundantly in the malignant parts of CXPA. The concept of CAFs is new, and the amount of this population was reportedly correlated with a poor prognosis in malignancy [ 20 ].…”

Section: Resultsmentioning

confidence: 99%

Increase in Chymase-Positive Mast Cells in Recurrent Pleomorphic Adenoma and Carcinoma Ex Pleomorphic Adenoma of the Parotid Gland

Kinoshita¹,

Jin²,

Higashino³

et al. 2021

IJMS

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Incomplete excision of pleomorphic adenoma (PA) may result in recurrent pleomorphic adenoma (RPA). Furthermore, long-term neglected PA may become carcinoma ex pleomorphic adenoma (CXPA). In the present study, the relationships between mast cell-derived chymase and these tumors were examined. The tumor tissues of PA consisted of either or both glandular and fibrotic structures. Histological features of RPA were almost similar to those of PA, except that they showed multinodular structures. CXPA is composed of a mixture of PA and carcinoma. The main stromal cells in PA were myofibroblasts, whereas fibroblasts constituted the main cellular portion in the stromal tissue of RPA. Cancer-associated fibroblasts (CAFs) were present abundantly in CXPA. With increased VEGF expression, neovascularization tended to increase in RPA or CXPA. Compared with PA, chymase-positive mast cells, as well as chymase gene expression, were increased in the tumor tissues from patients with RPA or CXPA. SCF, TGFβ1, and PCNA-positive staining was widely observed in these tumor tissues. The above results suggest that mast cell-derived chymase through its direct or cooperative effects with other mediators may participate in the pathophysiology of RPA and CXPA.

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“…CAFs represent one of the most abundant cell populations in the TME and contribute to tumor growth and dissemination through the release of growth factors and chemokines [ 115 ]. CAFs are, however, very heterogenous—diverse fibroblast subpopulations with distinct lineage origin and activation mechanisms have been identified in several solid cancers [ 116 , 117 , 118 , 119 ]. Four different CAF subpopulations (named CAF-S1, CAF-S2, CAF-S3, and CAF-S4) were identified by the same group in OC and BC based on multicolor flow cytometry analysis of the TME derived cells using antibodies against key fibroblast markers [ 120 , 121 ].…”

Section: Tg2 In Cancer-associated Fibroblasts (Cafs)mentioning

confidence: 99%

The Outside-In Journey of Tissue Transglutaminase in Cancer

Sima

Matei

Condello

2022

Cells

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Tissue transglutaminase (TG2) is a member of the transglutaminase family that catalyzes Ca2+-dependent protein crosslinks and hydrolyzes guanosine 5′-triphosphate (GTP). The conformation and functions of TG2 are regulated by Ca2+ and GTP levels; the TG2 enzymatically active open conformation is modulated by high Ca2+ concentrations, while high intracellular GTP promotes the closed conformation, with inhibition of the TG-ase activity. TG2’s unique characteristics and its ubiquitous distribution in the intracellular compartment, coupled with its secretion in the extracellular matrix, contribute to modulate the functions of the protein. Its aberrant expression has been observed in several cancer types where it was linked to metastatic progression, resistance to chemotherapy, stemness, and worse clinical outcomes. The N-terminal domain of TG2 binds to the 42 kDa gelatin-binding domain of fibronectin with high affinity, facilitating the formation of a complex with β-integrins, essential for cellular adhesion to the matrix. This mechanism allows TG2 to interact with key matrix proteins and to regulate epithelial to mesenchymal transition and stemness. Here, we highlight the current knowledge on TG2 involvement in cancer, focusing on its roles translating extracellular cues into activation of oncogenic programs. Improved understanding of these mechanisms could lead to new therapeutic strategies targeting this multi-functional protein.

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Characterising cancer-associated fibroblast heterogeneity in non-small cell lung cancer: a systematic review and meta-analysis

Cited by 32 publications

References 105 publications

CAFs Interacting With TAMs in Tumor Microenvironment to Enhance Tumorigenesis and Immune Evasion

CAFs Interacting With TAMs in Tumor Microenvironment to Enhance Tumorigenesis and Immune Evasion

Increase in Chymase-Positive Mast Cells in Recurrent Pleomorphic Adenoma and Carcinoma Ex Pleomorphic Adenoma of the Parotid Gland

The Outside-In Journey of Tissue Transglutaminase in Cancer

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