Dataset Information

CD30 Regulation of IL-13-STAT6 Pathway in Breast Implant-Associated Anaplastic Large Cell Lymphoma.

ABSTRACT:

Background

Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare, usually indolent CD30+ T-cell lymphoma with tumor cells, often surrounded by eosinophils, expressing IL-13 and pSTAT6.

Objectives

The aim of this study was to understand the unique tumor pathology and growth regulation of BIA-ALCL, leading to potential targeted therapies.

Methods

We silenced CD30 and analyzed its effect on IL-13 signaling and tumor cell viability. IL-13 signaling receptors of BIA-ALCL cell lines were evaluated by flow cytometry and pSTAT6 detected by immunohistochemistry. CD30 was deleted by CRISPR/Cas9 editing. Effects of CD30 deletion on transcription of IL-13 and IL-4, and phosphorylation of STAT6 were determined by real-time polymerase chain reaction and western blotting. The effect of CD30 deletion on p38 mitogen-activated protein kinase (MAPK) phosphorylation was determined. Suppression of IL-13 transcription by a p38 MAPK inhibitor was tested. Tumor cell viability following CD30 deletion and treatment with a pSTAT6 inhibitor were measured in cytotoxicity assays.

Results

BIA-ALCL lines TLBR1 and TLBR2 displayed signaling receptors IL-4Rα, IL-13Rα1 and downstream pSTAT6. Deletion of CD30 by CRISPR/Cas9 editing significantly decreased transcription of IL-13, less so Th2 cytokine IL-4, and phosphorylation of STAT6. Mechanistically, we found CD30 expression is required for p38 MAPK phosphorylation and activation, and IL-13-STAT6 signaling was reduced by an inhibitor of p38 MAPK in BIA-ALCL tumor cells. Tumor cell viability was decreased by silencing of CD30, and a specific inhibitor of STAT6, indicating STAT6 inhibition is cytotoxic to BIA-ALCL tumor cells.

Conclusions

These findings suggest reagents targeting the IL-13 pathway, pSTAT6 and p38 MAPK, may become useful for treating BIA-ALCL patients.

SUBMITTER: Kadin ME

PROVIDER: S-EPMC10208747 | biostudies-literature | 2023 Feb

REPOSITORIES: biostudies-literature

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Publications

CD30 Regulation of IL-13-STAT6 Pathway in Breast Implant-Associated Anaplastic Large Cell Lymphoma.

Kadin Marshall E ME Morgan John J Wei Wei W Song Zhihui Z Yang Yibin Y

Aesthetic surgery journal 20230201 2

<h4>Background</h4>Breast implant-associated anaplastic large cell lymphoma (BIA-ALCL) is a rare, usually indolent CD30+ T-cell lymphoma with tumor cells, often surrounded by eosinophils, expressing IL-13 and pSTAT6.<h4>Objectives</h4>The aim of this study was to understand the unique tumor pathology and growth regulation of BIA-ALCL, leading to potential targeted therapies.<h4>Methods</h4>We silenced CD30 and analyzed its effect on IL-13 signaling and tumor cell viability. IL-13 signaling recep ...[more]

PMID: 35999655

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Project description:IntroductionBreast implant-associated anaplastic large-cell lymphoma (BIA-ALCL) is a rare form of non-Hodgkin T-cell lymphoma associated with breast reconstruction post-mastectomy or cosmetic-additive mammoplasty. The increasing use of implants for cosmetic purposes is expected to lead to an increase in BIA-ALCL cases. This study investigated the main characteristics of the disease and the factors predicting BIA-ALCL onset in patients with and without an implant replacement.MethodsA quantitative analysis was performed by two independent researchers on cases extracted from 52 primary studies (case report, case series, and systematic review) published until April 2022 and searched in PubMed, Scopus, and Google-Scholar databases using "Breast-Implant" AND/OR "Associated" AND/OR "Anaplastic-Large-Cell-Lymphoma". The statistical significance was verified by Student's t-test for continuous variables, while Fisher's exact test was applied for qualitative variables. Cox model with time-dependent covariates was used to estimate BIA-ALCL's onset time. The Kaplan-Meier model allowed the estimation of the probability of survival after therapy according to breast implant exposure time.ResultsOverall, 232 patients with BIA-ALCL were extracted. The mean age at diagnosis was 55 years old, with a mean time to disease onset from the first implant of 10.3 years. The hazard of developing BIA-ALCL in a shorter time resulted significantly higher for patients not having an implant replacement (hazard ratio = 0.03; 95%CI: 0.005-0.19; p-value < 0.01). Patients with implant replacement were significantly older than patients without previous replacement at diagnosis, having a median time to diagnosis since the first implant of 13 years (7 years in patients without replacement); anyway, the median time to BIA-ALCL occurrence since the last implantation was equal to 5 years.DiscussionOur findings suggest that, in BIA-ALCL patients, the implant substitution and/or capsulectomy may delay the disease's onset. However, the risk of reoccurrence in an earlier time should be considered in these patients. Moreover, the time to BIA-ALCL onset slightly increased with age. Selection bias, lack of awareness, misdiagnosis, and limited data availability could be identified as limits of our study. An implant replacement should be considered according to a risk stratification approach to delay the BIA-ALCL occurrence in asymptomatic patients, although a stricter follow-up after the implant substitution should be recommended.Systematic review registrationhttps://www.crd.york.ac.uk/PROSPERO, identifier: CRD42023446726.

Dataset Information

CD30 Regulation of IL-13-STAT6 Pathway in Breast Implant-Associated Anaplastic Large Cell Lymphoma.

Background

Objectives

Methods

Results

Conclusions

Publications

CD30 Regulation of IL-13-STAT6 Pathway in Breast Implant-Associated Anaplastic Large Cell Lymphoma.

Similar Datasets

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