Carcinoma‐associated fibroblasts, its implication in head and neck squamous cell carcinoma: a mini review

Routray, Samapika; Sunkavali, A; Bari, KA

doi:10.1111/odi.12107

Cited by 25 publications

(15 citation statements)

References 72 publications

(68 reference statements)

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“…In the tumor microenvironment, the fibroblast is a specific cell type located in the stroma of cancer, namely cancer-associated fibroblast cells (CAFs). Accumulating evidence indicates that CAFs support the proliferation, migration and chemotherapy resistance of cancer cells by producing extracellular matrix, secreting cytokines, and activating signaling pathways in cancer cells (5,6). The adipocyte, another mesenchymal cell, stores energy and also secretes various adipokines and cytokines to promote tumor development.…”

Section: Introductionmentioning

confidence: 99%

DT-13 inhibits cancer cell migration by regulating NMIIA indirectly in the tumor microenvironment

Huang

Hou

et al. 2016

Oncology Reports

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Tumor metastasis is one of the main causes of mortality among patients with malignant tumors. Previous studies concerning tumor metastasis have merely focused on the cancer cells in the tumor. However, an increasing number of studies show that the tumor microenvironment plays a vital role in the progression of cancer, particularly in tumor metastasis. Since fibroblasts and adipocytes are two of the most representative mesenchymal cells in the tumor microenvironment, we established a hypoxia-induced cancer-associated fibroblast (CAF) model and a chemically induced adipocyte model to reveal the effect of the microenvironment on cancer development. In these models, the conditioned medium from the tumor microenvironment was found to significantly promote the migration of human lung cancer cell line 95D and regulate the expression of non-muscle myosin IIA (NMIIA), which is consistent with results in the published literature. Then, we confirmed the hypothesis that the tumor microenvironment can regulate NMIIA in cancer cells and facilitate migration by using the non-muscle myosin II inhibitor, blebbistatin. Thus, this is the first report that the tumor microenvironment can promote cancer cell migration by regulating the expression of NMIIA. Our present data also indicated that DT-13, the saponin monomer 13 of dwarf lilyturf tuber, inhibited cancer cell migration in the tumor microenvironment model. Further results showed that DT-13 exhibited anti-migratory effects by inhibiting the c-raf/ERK1/2 signaling pathway. Consequently, our research confirmed that DT-13 significantly inhibited 95D cell migration in vitro, indicating the potential anti-metastatic effect of DT-13 on lung cancer and the scientific basis for drug development.

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Section: Introductionmentioning

confidence: 99%

DT-13 inhibits cancer cell migration by regulating NMIIA indirectly in the tumor microenvironment

Huang

Hou

et al. 2016

Oncology Reports

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“…[16][17][18][19] It was recently documented that CAFs from several solid tumors harbored the ability to partially promote the proliferation, invasion, and metastasis of corresponding tumor cells. [20][21][22][23] All of these studies were performed using cell lines established from solid tumors, and these cell lines clearly harbored vigorous capacities for proliferation and invasion in vitro. However, it is not clear whether CAFs are able to promote the primary growth of cancer cells in solid tumor specimens nor to what extent.…”

Section: Discussionmentioning

confidence: 99%

The primary growth of laryngeal squamous cell carcinoma cells in vitro is effectively supported by paired cancer-associated fibroblasts alone

Wang

Guo

et al. 2017

Tumour Biol.

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Most primarily cultured laryngeal squamous cell carcinoma cells are difficult to propagate in vitro and have a low survival rate. However, in our previous work to establish a laryngeal squamous cell carcinoma cell line, we found that laryngeal cancer-associated fibroblasts appeared to strongly inhibit the apoptosis of primarily cultured laryngeal squamous cell carcinoma cells in vitro. In this study, we investigated whether paired laryngeal cancer-associated fibroblasts alone can effectively support the growth of primarily cultured laryngeal squamous cell carcinoma cells in vitro. In all, 29 laryngeal squamous cell carcinoma specimens were collected and primarily cultured. The laryngeal squamous cell carcinoma cells were separated from cancer-associated fibroblasts by differential trypsinization and continuously subcultured. Morphological changes of the cultured laryngeal squamous cell carcinoma cells were observed. Immunocytofluorescence was used to authenticate the identity of the cancer-associated fibroblasts and laryngeal squamous cell carcinoma cells. Flow cytometry was used to quantify the proportion of apoptotic cells. Western blot was used to detect the protein levels of caspase-3. Enzyme-linked immunosorbent assay was used to detect the levels of chemokine (C-X-C motif) ligand 12, chemokine (C-X-C motif) ligand 7, hepatocyte growth factor, and fibroblast growth factor 1 in the supernatants of the laryngeal squamous cell carcinoma and control cells. AMD3100 (a chemokine (C-X-C motif) receptor 4 antagonist) and an anti-chemokine (C-X-C motif) ligand 7 antibody were used to block the tumor-supporting capacity of cancer-associated fibroblasts. Significant apoptotic changes were detected in the morphology of laryngeal squamous cell carcinoma cells detached from cancer-associated fibroblasts. The percentage of apoptotic laryngeal squamous cell carcinoma cells and the protein levels of caspase-3 increased gradually in subsequent subcultures. In contrast, no significant differences in the proliferation capacity of laryngeal squamous cell carcinoma cells cocultured with cancer-associated fibroblasts were detected during subculturing. High level of chemokine (C-X-C motif) ligand 12 was detected in the culture supernatant of cancer-associated fibroblasts. The tumor-supporting effect of cancer-associated fibroblasts was significantly inhibited by AMD3100. Our findings demonstrate that the paired laryngeal cancer-associated fibroblasts alone are sufficient to support the primary growth of laryngeal squamous cell carcinoma cells in vitro and that the chemokine (C-X-C motif) ligand 12/chemokine (C-X-C motif) receptor 4 axis is one of the major contributors.

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“…Myofibroblasts are not only key cells in fibrosis, their importance has been long established in cancer where the presence of myofibroblasts in the stroma as “cancer associated fibroblasts” facilitates tumor development and has often been associated with inflammation, cell invasion, high grade malignancy, and poor prognosis . Myofibroblasts are enriched in stroma from prostate cancer as compared with benign prostatic hyperplasia, and associated with the leading edge of carcinomas . They produce MMP, cytokines (IL8, VEGF), and chemokines (CXCL12) to promote cancer proliferation, tumor invasion, and neoangiogenesis (reviewed in).…”

Section: Discussionmentioning

confidence: 99%

Master regulators in primary skin fibroblast fate reprogramming in a human ex vivo model of chronic wounds

Noizet

Lagoutte

Gratigny

et al. 2016

Wound Repair Regeneration

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Fibroblasts are important players in regulating tissue homeostasis. In the dermis, they are involved in wound healing where they differentiate into contractile myofibroblasts leading to wound closure. In nonhealing chronic wounds, fibroblasts fail to undertake differentiation. We established and used a human ex vivo model of chronic wounds where fibroblasts can undergo normal myofibroblast differentiation, or take on a nondifferentiable pathological state. At the whole genome scale, we identified the genes that are differentially regulated in these two cell fates. By coupling the search of evolutionary conserved regulatory elements with global gene network expression changes, we identified transcription factors (TF) potentially involved in myofibroblast differentiation, and constructed a network of relationship between these key factors. Among these, we found that TCF4, SOX9, EGR2, and FOXS1 are major regulators of fibroblast to myofibroblast differentiation. Conversely, down-regulation of MEOX2, SIX2, and MAF causes reprogramming of fibroblasts to myofibroblasts even in absence of TGF-b, the natural inducer of myofibroblast differentiation. These results provide insight into the fibroblast differentiation program and reveal a TF network essential for cellular reprogramming. They could lead to the development of new therapeutics to treat fibroblast-related human pathologies.

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Carcinoma‐associated fibroblasts, its implication in head and neck squamous cell carcinoma: a mini review

Cited by 25 publications

References 72 publications

DT-13 inhibits cancer cell migration by regulating NMIIA indirectly in the tumor microenvironment

DT-13 inhibits cancer cell migration by regulating NMIIA indirectly in the tumor microenvironment

The primary growth of laryngeal squamous cell carcinoma cells in vitro is effectively supported by paired cancer-associated fibroblasts alone

Master regulators in primary skin fibroblast fate reprogramming in a human ex vivo model of chronic wounds

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