Arginase is involved in cervical lesions progression and severity

M, Souid; Ghedira, Randa; Souissi, Sameh; Bouzgarrou, Nadia; Gabbouj, Sallouha; Shini-Hadhri, Salwa; Rhim, Mohamed-Saleh; Boukadida, A.; Toumi, Dhekra; Faleh, Raja; Bouaouina, Noureddine; Zakhama, Abdelfattah; Hassen, Elham

doi:10.1016/j.imbio.2022.152189

Cited by 5 publications

(4 citation statements)

References 38 publications

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“…We also demonstrate that BC patients positive for ARG2 had worse BMFS and OS, highlighting the clinical importance of ARG2 in aggressive BC and potentially in the development of BCBM. Our data agree with other studies showing the prognostic potential of ARG2, 22 , 43 , 44 , 45 while a recent study showed that ARG2 promotes melanoma progression and metastasis through STAT3 signalling, also involved in BM. 46 , 47 Since arginase has been identified as a potential biomarker of disease progression, investigating the therapeutic efficacy of arginase inhibitors as monotherapy or in combination with PD-1/PD-L1 inhibitors has been of great research interest 38 , 40 , 48 , 49 , 50 , 51 , 52 and a number of clinical trials are ongoing ( Supplementary Table S2 , available at https://doi.org/10.1016/j.esmoop.2022.100636 ) in advanced solid tumours and glioblastoma.…”

Section: Discussionsupporting

confidence: 93%

Characterisation of the immune microenvironment of primary breast cancer and brain metastasis reveals depleted T-cell response associated to ARG2 expression

Giannoudis

Varešlija²,

Sharma

et al. 2022

ESMO Open

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Section: Discussionsupporting

confidence: 93%

Characterisation of the immune microenvironment of primary breast cancer and brain metastasis reveals depleted T-cell response associated to ARG2 expression

Giannoudis

Varešlija²,

Sharma

et al. 2022

ESMO Open

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“…The fibrosis of tumours is similar to that of the lens to some extent. Available data have demonstrated the abnormally high expression and activity of arginase in gastric cancer [ 39 ], breast cancer cells [ 40 , 41 ], malignant skin tumours [ 42 ], and cervical cancer [ 43 ]. Tumours in ARG1 KO mice were 50% smaller than those in wild-type mice [ 44 ].…”

Section: Discussionmentioning

confidence: 99%

Arginase-1 promotes lens epithelial-to-mesenchymal transition in different models of anterior subcapsular cataract

Li,

Wang,

Shi

et al. 2023

Cell Commun Signal

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Background Arginase-1 (ARG1) promotes collagen synthesis and cell proliferation. ARG1 is highly expressed in various tumour cells. The mechanisms of ARG1 in epithelial-to-mesenchymal transition (EMT)-associated cataracts were studied herein. Methods C57BL/6 mice, a human lens epithelial cell line (HLEC-SRA01/04), and human lens capsule samples were used in this study. The right lens anterior capsule of the mouse eye was punctured through the central cornea with a 26-gauge hypodermic needle. Human lens epithelial cells (HLECs) were transfected with ARG1-targeted (siARG1) or negative control siRNA (siNC). For gene overexpression, HLECs were transfected with a plasmid bearing the ARG1 coding sequence or an empty vector. Medium containing 0.2% serum with or without transforming growth factor beta-2 (TGF-β2) was added for 6 or 24 h to detect mRNA or protein, respectively. The expression of related genes was measured by quantitative real-time polymerase chain reaction (RT–qPCR), western blotting, and immunohistochemical staining. Transwell assays and wound healing assays were used to determine cell migration. Cell proliferation, superoxide levels, nitric oxide (NO) levels, and arginase activity were estimated using Cell Counting Kit-8 assays, a superoxide assay kit, an NO assay kit, and an arginase activity kit. Results ARG1, alpha-smooth muscle actin (α-SMA), fibronectin, and Ki67 expression increased after lens capsular injury, while zonula occludens-1 (ZO-1) expression decreased. Fibronectin and collagen type I alpha1 chain (collagen 1A1) expression increased, and cell migration increased significantly in ARG1-overexpressing HLECs compared with those transfected with an empty vector after TGF-β2 treatment. These effects were reversed by ARG1 knockdown. The arginase-related pathway plays an important role in EMT. mRNAs of enzymes of the arginase-related pathway were highly expressed after ARG1 overexpression. ARG1 knockdown suppressed these expression changes. Numidargistat (CB-1158) dihydrochloride (CB-1158), an ARG1 inhibitor, suppressed TGF-β2-induced anterior subcapsular cataract (ASC) by reducing the proliferation of lens epithelial cells (LECs) and decreasing fibronectin, α-SMA, collagen 1A1, and vimentin expression. Compared with that in nonanterior subcapsular cataract (non-ASC) patients, the expression of ARG1, collagen 1A1, vimentin, fibronectin, and Ki67 was markedly increased in ASC patients. Conclusions ARG1 can regulate EMT in EMT-associated cataracts. Based on the pathogenesis of ASC, these findings are expected to provide new therapeutic strategies for patients. Graphical abstract

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“…High IL-10 levels correlate with amplified arginase activity, decreasing L-arginine levels but increasing L-Arg metabolite levels, which is crucial to tumor growth [88][89][90][91]. HPV+ women, with either precancerous cervical lesions or CC, have elevated arginase levels, indicating persistent immunosuppression and a tumor-supportive immune environment [92]. Furthermore, indoleamine 2,3-dioxygenase (IDO) and tryptophan 2,3-dioxygenase (TDO) are also critical players in CC immunopathogenesis [93,94].…”

Section: Immunopathogenesismentioning

confidence: 99%

TIME Is Ticking for Cervical Cancer

Kumar

Bauer

Stewart

2023

Biology

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Cervical cancer (CC) is a major health problem among reproductive-age females and comprises a leading cause of cancer-related deaths. Human papillomavirus (HPV) is the major risk factor associated with CC incidence. However, lifestyle is also a critical factor in CC pathogenesis. Despite HPV vaccination introduction, the incidence of CC is increasing worldwide. Therefore, it becomes critical to understand the CC tumor immune microenvironment (TIME) to develop immune cell-based vaccination and immunotherapeutic approaches. The current article discusses the immune environment in the normal cervix of adult females and its role in HPV infection. The subsequent sections discuss the alteration of different immune cells comprising CC TIME and their targeting as future therapeutic approaches.

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Arginase is involved in cervical lesions progression and severity

Cited by 5 publications

References 38 publications

Characterisation of the immune microenvironment of primary breast cancer and brain metastasis reveals depleted T-cell response associated to ARG2 expression

Characterisation of the immune microenvironment of primary breast cancer and brain metastasis reveals depleted T-cell response associated to ARG2 expression

Arginase-1 promotes lens epithelial-to-mesenchymal transition in different models of anterior subcapsular cataract

TIME Is Ticking for Cervical Cancer

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