Immunohistochemical Characterization of Cancer-associated Fibroblasts in Oral Squamous Cell Carcinoma

Dourado, Raísa Cavalcante; Porto, Lia Pontes Arruda; Henriques, Águida Cristina Gomes; Cerqueira, Paloma Souza Gonçalves; Santos, Jean Nunes dos; Ramalho, Luciana Maria Pedreira; Xavier, Flávia Caló Aquino

doi:10.1097/pai.0000000000000486

Cited by 14 publications

(6 citation statements)

References 26 publications

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“…The increased stromal stiffness aggravates hypoxic TME, which promotes neutrophil polarization and inhibits its apoptosis ( 32 ). Besides histological morphology, the CAF immunophenotypes are variable, and the level of α-SMA expression is higher in the immature CAF subtype than in the mature CAF subtype ( 33 ), as we have found. We further demonstrated that IL-8 was highly expressed in mature CAFs than in immature CAFs; that mature CAFs correlated with TANs in SM tumors, especially in SM2 tumors; and that mature CAFs were significantly associated with LNM in SM2 tumors.…”

Section: Discussionsupporting

confidence: 69%

Tumor-Associated Neutrophils Can Predict Lymph Node Metastasis in Early Gastric Cancer

et al. 2020

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The consensus of endoscopic therapy for early gastric cancer (EGC) mainly depends on its clinicopathological features. However, the roles of tumor-associated neutrophils (TANs) in EGC remain uncertain. Here, we explored its predictive role for lymph node metastasis (LNM) in EGC. Three hundred twenty-two patients who underwent radical gastrectomy for EGC were enrolled. Preoperative peripheral blood was used to analyze the neutrophil-to-lymphocyte ratio (NLR), and the different status of TANs was determined by hematoxylin-and-eosin staining (H&E) and immunohistochemistry (IHC). TANs, rather than NLR, were positively associated with tumor size, Lauren classification, lymphovascular invasion (LVI), and LNM. Univariate analysis revealed that TANs were associated with LNM as well as tumor size, depth of invasion, Lauren classification, histological classification, LVI, and perineural invasion. In addition to histological classification and LVI, TANs were found to be an independent risk factor for LNM in EGC (P = 0.013). Stratification analysis by depth of invasion showed LVI in SM1 tumor, and both LVI and TANs (P = 0.042) in SM2 tumor were independent risk factors for LNM. In conclusion, TANs in EGC can predict LNM, and TANs may help to estimate LNM precisely in addition to the current criteria.

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Section: Discussionsupporting

confidence: 69%

Tumor-Associated Neutrophils Can Predict Lymph Node Metastasis in Early Gastric Cancer

et al. 2020

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“…As the predominant component of the tumor stroma, CAFs are known to be regulators of tumor invasion, metastasis and chemoresistance via activating the crosstalk with cancer cells (26,27). The positive expression of α-SMA in stromal broblasts represents a suitable immunophenotype of CAFs (28). Indeed, our present study found the proportional number of broblasts in the stroma was positively associated with the progression of HNSCC tumor.…”

Section: Discussionsupporting

confidence: 62%

TERT drives fibroblasts reprogramming to promote the invasion of head and neck squamous cell carcinoma via transferring of exosomal MET protein

Yang

Zhang

Tao

et al. 2020

Preprint

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Background Head and neck squamous cell carcinoma (HNSCC) is characterized by the highly infiltrative capacity and invariably aggressive feature, the oncogenic functions of TERT in cell transformation and tumor progression have well been elucidated; however, very little is known about the effect of TERT on the microenvironment during the tumorigenesis of HNSCC. Methods An bioinformatics analysis of TERT was firstly performed from TCGA dataset, and the correlation of TERT activity with tumor microenvironment (TME) was assessed on the basis of the analysis of HNSCC patient specimen in vivo and in vitro co-culture experiments. We next conducted an cDNA microarray analysis and identified the TERT-driven key molecule MET in the functionally regulation of tumor-fibroblasts crosstalk. Furthermore, the phenotypic and functional alteration of primary fibroblasts were detected by a series of molecular biology experiments following treatment with TERT overexpressed/silenced HNSCC cell-derived exosomes or MET transfection, respectively, and the underlying intracellular signaling pathway was tested. Finally, the effect of programming fibroblasts on the aggressive behavior of HNSCC cells were evaluated in vivo and in vitro assays. Results Here, we found that TERT was significantly elevated in HNSCC tissues in comparison with normal mucosa tissues, and its level was increased along with malignant progression of the tumor. Furthermore, the activated TERT enhanced cancer-fibroblasts interaction and promoted cancer-associated fibroblasts (CAFs) formation in TME. Mechanistically, TERT-driven normal fibroblast reprogramming into CAFs is exosomal MET dependent, activated TERT could physically interact with MET protein and increase exosomal MET protein released from HNSCC cells, which promotes the intercellular trafficking of MET into fibroblasts and consequently activated AKT and ERK signaling pathways, resulting in primary fibroblast reprogramming through increased cell proliferation, migration and elevation of the pro-inflammatory gene signature. More importantly, the programmed fibroblasts in turn promote the migration and invasion of HNSCC cells. Conclusions Our results unveil a novel role of TERT-driven modulation of the TME, which may offer new opportunities for potential therapeutic strategies targeting HNSCC development.

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“…Therefore, the expression of vimentin, α-SMA and cytokeratin was detected to identify the immunophenotype of the primarily cultured fibroblasts. α-SMA is not only a widely used marker for identifying CAFs, but is also an independent prognostic marker, which significantly correlated with metastasis, recurrence and mortality in oral squamous cell carcinoma (OSCC) (26–28). It has been reported that the expression of α-SMA in PTFs is variable in different organs (29,30).…”

Section: Discussionmentioning

confidence: 99%

Cancer associated ﬁbroblasts are distinguishable from peri‑tumor ﬁbroblasts by biological characteristics in TSCC

Zhang

et al. 2019

Oncol Lett

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The aim of the present study was to investigate the differential biological characteristics between cancer-associated fibroblasts (CAFs) and peri-tumor fibroblasts (PTFs) in tongue squamous cell carcinoma (TSCC). The primary CAFs and PTFs from TSCC were obtained and purified. Cell morphology was observed, and the expression of α-smooth muscle actin (α-SMA), vimentin and cytokeratin 19 (CK19) was detected by immunohistochemistry (IHC). The percentage of α-SMA positive cells in CAFs and PTFs was calculated separately, and α-SMA expression was further confirmed by western blot analysis. Cell viability and the expression of matrix metalloproteinase 2 (MMP2), stromal cell derived factor1 (SDF-1) and transforming growth factor β1 (TGFβ1) in the purified fibroblasts was detected separately. CAFs and PTFs were attained and purified. Compared with PTFs, CAFs were long-fusiform shaped cells with reduced cytoplasm and variable size. CAFs crowded together in a disorderly manner when the cell density was increased, but this phenomenon did not occur with PTFs. IHC results verified that there was no significant difference between CAFs and PTFs in the percentage of cells staining positive for CK19 and vimentin (P>0.05); the percentage of positive staining cells for α-SMA in CAFs was significantly higher compared with that in PTFs (P<0.001) Western blot analysis showed that α-SMA expression in CAFs was 4.3-fold higher compared with that in PTFs (P<0.001). A Cell Counting Kit-8 assay indicated that the viability of CAFs increased significantly compared with that in the PTFs (P<0.05). Reverse transcription-quantitative polymerase chain reaction and ELISA analysis showed that the expression of MMP2, SDF-1 and TGF β1 in CAFs was higher compared with that in PTFs (P<0.05). CAFs are distinguishable from PTFs with respect to their morphology, cellular phenotype, cell viability and pro-carcinogenic cytokine expression.

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Immunohistochemical Characterization of Cancer-associated Fibroblasts in Oral Squamous Cell Carcinoma

Cited by 14 publications

References 26 publications

Tumor-Associated Neutrophils Can Predict Lymph Node Metastasis in Early Gastric Cancer

Tumor-Associated Neutrophils Can Predict Lymph Node Metastasis in Early Gastric Cancer

TERT drives fibroblasts reprogramming to promote the invasion of head and neck squamous cell carcinoma via transferring of exosomal MET protein

Cancer associated ﬁbroblasts are distinguishable from peri‑tumor ﬁbroblasts by biological characteristics in TSCC

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