Regional atrophy, cellular plasticity, and regenerative potential in irradiated murine salivary glands.

IF 2.7 3区医学 Q3 ONCOLOGY

Acta Oncologica Pub Date : 2025-07-23 DOI:10.2340/1651-226X.2025.44012

Inga Solgård Juvkam, Olga Zlygosteva, Olaf Joseph Franciscus Schreurs, Nina Jeppesen Edin, Hilde Kanli Galtung, Eirik Malinen, Tine Merete Søland

{"title":"Regional atrophy, cellular plasticity, and regenerative potential in irradiated murine salivary glands.","authors":"Inga Solgård Juvkam, Olga Zlygosteva, Olaf Joseph Franciscus Schreurs, Nina Jeppesen Edin, Hilde Kanli Galtung, Eirik Malinen, Tine Merete Søland","doi":"10.2340/1651-226X.2025.44012","DOIUrl":null,"url":null,"abstract":"Background and purpose: Radiotherapy of head and neck cancer may cause detrimental late side effects such as fibrosis and hyposalivation. We investigated mouse salivary glands after fractionated irradiation, with the aim to elucidate cellular plasticity and potential regeneration.Methods: 12-week-old female C57BL/6JRj mice were irradiated with X-rays to a total dose of 66 Gy, given in 10 fractions over 5 days. The radiation field covered the oral cavity and major salivary glands. The submandibular (SMG), sublingual (SLG), and parotid glands (PG) were dissected at day 100 after finishing irradiation. Using different histological staining techniques, morphological, cellular, and molecular changes were investigated in irradiated and control SMG, SLG, and PG.Results: Atrophy of acinar cells was observed in irradiated SMG and SLG, but not in PG. Surprisingly, the acinar atrophy was confined to one region of each irradiated gland. These atrophic regions showed distinct cellular and molecular compositions compared to non-atrophic regions and control glands. Increased expression of the ductal cell markers keratin 5 and 19 (K5 and K19), along with increased percentages of proliferating myofibroblasts, fibroblasts, leukocytes, and acinar cells (Nkcc1+) were observed in the atrophic regions compared to controls. In addition, some of the K19+ and K5+ duct-like cells also co-expressed Nkcc1.Interpretation: Through a detailed histological assessment of the cellular and molecular changes in the major salivary glands of irradiated mice, we observed signs of cellular plasticity where ductal cells adopt an acinar cell phenotype upon irradiation. This suggests a regenerative potential of salivary glands after irradiation.","PeriodicalId":7110,"journal":{"name":"Acta Oncologica","volume":"64 ","pages":"927-938"},"PeriodicalIF":2.7000,"publicationDate":"2025-07-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://www.ncbi.nlm.nih.gov/pmc/articles/PMC12305691/pdf/","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Acta Oncologica","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.2340/1651-226X.2025.44012","RegionNum":3,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q3","JCRName":"ONCOLOGY","Score":null,"Total":0}

引用次数: 0

Abstract

Background and purpose: Radiotherapy of head and neck cancer may cause detrimental late side effects such as fibrosis and hyposalivation. We investigated mouse salivary glands after fractionated irradiation, with the aim to elucidate cellular plasticity and potential regeneration.

Methods: 12-week-old female C57BL/6JRj mice were irradiated with X-rays to a total dose of 66 Gy, given in 10 fractions over 5 days. The radiation field covered the oral cavity and major salivary glands. The submandibular (SMG), sublingual (SLG), and parotid glands (PG) were dissected at day 100 after finishing irradiation. Using different histological staining techniques, morphological, cellular, and molecular changes were investigated in irradiated and control SMG, SLG, and PG.

Results: Atrophy of acinar cells was observed in irradiated SMG and SLG, but not in PG. Surprisingly, the acinar atrophy was confined to one region of each irradiated gland. These atrophic regions showed distinct cellular and molecular compositions compared to non-atrophic regions and control glands. Increased expression of the ductal cell markers keratin 5 and 19 (K5 and K19), along with increased percentages of proliferating myofibroblasts, fibroblasts, leukocytes, and acinar cells (Nkcc1+) were observed in the atrophic regions compared to controls. In addition, some of the K19+ and K5+ duct-like cells also co-expressed Nkcc1.

Interpretation: Through a detailed histological assessment of the cellular and molecular changes in the major salivary glands of irradiated mice, we observed signs of cellular plasticity where ductal cells adopt an acinar cell phenotype upon irradiation. This suggests a regenerative potential of salivary glands after irradiation.

查看原文本刊更多论文

受辐射小鼠唾液腺的局部萎缩、细胞可塑性和再生潜能。

背景与目的：头颈部肿瘤放疗可引起晚期不良副作用，如纤维化和肝纤维化。我们研究了经分级辐照的小鼠唾液腺，目的是阐明细胞的可塑性和潜在的再生。方法：对12周龄雌性C57BL/6JRj小鼠进行x射线照射，总剂量为66 Gy，分10次照射，持续5天。辐射场覆盖口腔和主要唾液腺。照射结束后第100天，分别切除颌下腺（SMG）、舌下腺（SLG）和腮腺（PG）。使用不同的组织学染色技术，研究了SMG、SLG和PG在辐照和对照下的形态学、细胞和分子变化。结果：在SMG和SLG中观察到腺泡细胞萎缩，而PG中没有。令人惊讶的是，腺泡萎缩局限于每个辐照腺体的一个区域。与非萎缩区和控制腺体相比，这些萎缩区显示出不同的细胞和分子组成。与对照组相比，萎缩区导管细胞标记物角蛋白5和19 （K5和K19）的表达增加，肌成纤维细胞、成纤维细胞、白细胞和腺泡细胞（Nkcc1+）的增殖百分比增加。此外，部分K19+和K5+导管样细胞也共表达Nkcc1。解释：通过对辐照小鼠主要唾液腺细胞和分子变化的详细组织学评估，我们观察到细胞可塑性的迹象，其中导管细胞在辐照下采用腺泡细胞表型。这表明放射后唾液腺具有再生潜能。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

求助全文

约1分钟内获得全文求助全文

来源期刊

Acta Oncologica 医学-肿瘤学

CiteScore

4.30

自引率

3.20%

发文量

301

审稿时长

3 months

期刊介绍： Acta Oncologica is a journal for the clinical oncologist and accepts articles within all fields of clinical cancer research. Articles on tumour pathology, experimental oncology, radiobiology, cancer epidemiology and medical radio physics are also welcome, especially if they have a clinical aim or interest. Scientific articles on cancer nursing and psychological or social aspects of cancer are also welcomed. Extensive material may be published as Supplements, for which special conditions apply.