{"title":"Discovery of nuclear cavities in Epstein-Barr virus-infected cells","authors":"Shinji Shimada , Hideya Kawasaki , Hiroto Katoh , Shumpei Ishikawa","doi":"10.1016/j.acthis.2025.152253","DOIUrl":"10.1016/j.acthis.2025.152253","url":null,"abstract":"<div><div>Approximately 90 % of humans are infected with the Epstein-Barr virus (EBV); however, most do not develop neoplastic lesions. Despite various investigations, the underlying reasons remain largely unknown. Therefore, we aimed to address this question through morphological observations to identify the ultrastructural alterations occurring in EBV-infected cells. EBV-positive cells from legacy lymph node specimens obtained from patients with HIV and modern fresh specimens of aberrantly proliferating human EBV-positive lymphocytes in a patient-derived xenograft (PDX) of immunodeficient mouse were examined. By utilizing a special technique that allowed us to observe exactly the same specimen using both optical and electron microscopy, we were able to detect a peculiar phenomenon in EBV-infected cells. EBV-infected lymphocytes occasionally exhibited nuclear cavities, a finding that was confirmed in multiple specimens from both patients with HIV and the PDX model. It was suggested that EBV-infected cells may activate cell death pathways, based on the protein expression patterns of p53 and FAS. Taken together, these results indicated that nuclear cavity formation appeared to be a characteristic morphological alteration associated with EBV infection. Further research could clarify the potential relationship between nuclear cavities and cellular biology in EBV-infected cells, possibly shedding light on the mechanisms that prevent EBV-infected cells from progressing to tumor formation.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 2","pages":"Article 152253"},"PeriodicalIF":2.3,"publicationDate":"2025-04-19","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143848641","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta histochemicaPub Date : 2025-04-18DOI: 10.1016/j.acthis.2025.152256
Gabriella Meier Bürgisser, Pietro Giovanoli, Maurizio Calcagni, Johanna Buschmann
{"title":"Comparison of collagen I and collagen III immunohistochemistry with Herovici staining in various rabbit organs","authors":"Gabriella Meier Bürgisser, Pietro Giovanoli, Maurizio Calcagni, Johanna Buschmann","doi":"10.1016/j.acthis.2025.152256","DOIUrl":"10.1016/j.acthis.2025.152256","url":null,"abstract":"<div><div>Collagen I and III distribution is not only crucial to assess the status of healing wounds, but also to characterise healthy connective tissue and pathological extracellular matrix composition. In this technical note, we have therefore compared the dual-coloured Herovici staining, indicating pink collagen I and blue collagen III in serial sections with immunohistochemistry (IHC) labellings for collagen I and III, respectively. Furthermore, we used, chromogenic DAB for IHC labelling. Seven different organs of a healthy New Zealand white rabbit were collected for this purpose, including kidney, liver, tonsil, tongue, duodenum, heart, and brain, respectively. A dual-coloured staining like Herovici turned out to be as good as two single-colour labellings utilising IHC. In some cases, co-localisation and extent of collagen I and III expression could be qualitatively visualised better using Herovici, with gradients of blue-violet-pink, than by mere comparison of labelling intensities side by side in two different sections, although taken at the same place as serial sections. Nevertheless, a quantitative analysis of the Collagen I-to-III ratio revealed no significant differences between these two approaches to assess the extracellular matrix composition. From these comparisons, we conclude that a Herovici staining is recommended as a valuable alternative staining to collagen I and III IHC; and it may act as a fast and cheap preliminary staining method. These findings encourage researchers focusing on ECM composition of the experimental rabbit tissue to use Herovici staining to determine the ratio of the extracellular collagen I and III expression.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 2","pages":"Article 152256"},"PeriodicalIF":2.3,"publicationDate":"2025-04-18","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143843744","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Fluorescent strategy for detection of uracil-DNA glycosylase activity based on isothermal amplification triggered by ligase","authors":"Pansong Zhang , Fangfang He , Xin Chang , Chenxia Ren","doi":"10.1016/j.acthis.2025.152252","DOIUrl":"10.1016/j.acthis.2025.152252","url":null,"abstract":"<div><div>Uracil-DNA glycosylase (UDG) plays a key role in the base repair system, and detecting its enzymatic activity is crucial for early disease diagnosis. A rapid method for detecting UDG was developed, utilizing amplification initiated by a ligation reaction. A DNA probe modified with uracil was utilized to ligate two free DNA strands to form a newly generated DNA strand. This triggers a nicking enzyme-assisted amplification reaction, resulting in the production of single-stranded DNA (ssDNA). Then, the amplified ssDNA triggered the molecular beacons to emit fluorescence. However, the addition of UDG results in the removal of uracil from the DNA probe strand, leaving abasic site (AP site). After heat denaturation, this site was destroyed, preventing subsequent ligation or amplification reactions, resulting in the absence of fluorescence. The findings of our study indicate that the addition of UDG at concentrations exceeding 0.5 U/mL resulted in complete suppression of fluorescence intensity, reaching a value of 0. Conversely, in the absence of the UDG enzyme or upon the addition of other enzymes and proteins such as HAAG, EndoIV and BSA, the fluorescence intensity of the system remains unaffected, achieving 100 % intensity within 5–20 min. This study presents a rapid method for assessing UDG activity that could be valuable for early disease diagnosis in the future.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 2","pages":"Article 152252"},"PeriodicalIF":2.3,"publicationDate":"2025-04-16","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143838018","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Immunohistochemistry and machine learning study of DNA replication-associated proteins in uterine epithelial tumors and precursor lesions","authors":"Takumi Urata , Fumikazu Kimura , Kengo Ohshima , Koyo Ikehata , Masahiro Yamaguchi , Keiko Ishii","doi":"10.1016/j.acthis.2025.152251","DOIUrl":"10.1016/j.acthis.2025.152251","url":null,"abstract":"<div><div>Endometrioid adenocarcinoma (EA) has been on the increase in recent years in developed countries. Early detection of endometrioid adenocarcinoma in the endometrial corpus is crucial for patient prognosis and early treatment, although their distinction can sometimes be challenging. In this study, we focused on DNA replication-related proteins through immunohistochemical analysis and investigated whether the discrimination between EA and their precursor lesions is achievable using machine learning techniques. The research utilized tissue specimens from 100 cases, including EA of different grades (Grade 1; G1, Grade 2; G2, Grade 3; G3) and their precursor lesions (endometrial hyperplasia without atypia; EH, endometrial atypical hyperplasia: AH). Immunohistochemical analysis of DNA replication-related proteins, such as ORC1, Cdt1, Cdc6, MCM7, Cdc7, and Geminin, was conducted for each case, measuring the Labeling Index (LI) and optical density (OD) of protein expression. Furthermore, we performed statistical significance tests and machine learning -discriminant analysis using LI and OD as inputs, employing non-linear Support Vector Machines (NSVM). The NSVM discriminant analysis demonstrated the accuracy of over 85 % between EH and each differentiation grade of EA, the accuracy is also similar for AH and each differentiation grade of EA. In addition, changing the combination of DNA replication-related proteins used for discrimination resulted in a high accuracy (95–100 %). A discriminant analysis with NSVM using the LI and OD of DNA replication-related proteins may enable the differentiation of EA from its precursor lesions.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 2","pages":"Article 152251"},"PeriodicalIF":2.3,"publicationDate":"2025-04-11","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143816633","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta histochemicaPub Date : 2025-04-05DOI: 10.1016/j.acthis.2025.152250
Tania M. Cortázar , Nohora A. Vega , Jinneth Acosta , Edgar A. Reyes-Montaño , Manuel A. Ballen-Vanegas , Orlando Ricaurte
{"title":"Galactia lindenii lectin type-II: Its potential use in thyroid cancer diagnosis","authors":"Tania M. Cortázar , Nohora A. Vega , Jinneth Acosta , Edgar A. Reyes-Montaño , Manuel A. Ballen-Vanegas , Orlando Ricaurte","doi":"10.1016/j.acthis.2025.152250","DOIUrl":"10.1016/j.acthis.2025.152250","url":null,"abstract":"<div><div><em>Galactia lindenii</em> lectin type-II (GLL-II) belongs to the group of the legume lectins. The present study investigated the GLL-II staining patterns in histological sections of neoplastic and non-neoplastic thyroid tissues. Besides, hemagglutination assays (HA) using the GLL-II on red blood cells of different glycomic profiles were performed, complementing previous results. The differential staining in Papillary Thyroid Cancer, Invasive Encapsulated Follicular Variant Papillary Thyroid Carcinoma, Hashimoto's thyroiditis, and non-neoplastic thyroid with goiter changes, together with the HA results, allowed us to propose the potential utility of GLL-II as part of lectin platforms used to discriminate between human thyroid pathological samples from normal ones. The present study shed light on potential applications of GLL-II in determining alterations of glycosylation patterns in specific cells, tissues, or body fluids, as well as glycotopes biomarkers of healthy or pathological conditions.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 2","pages":"Article 152250"},"PeriodicalIF":2.3,"publicationDate":"2025-04-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143783394","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"OA","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta histochemicaPub Date : 2025-03-22DOI: 10.1016/j.acthis.2025.152249
Lei Huang , Xiaobin Zeng , Kaimin Xiao , Sen Tang , Kuo Sun
{"title":"Silencing Livin gene expression by RNA interference enhanced the chemotherapeutic sensitivity of drug-resistant osteosarcoma cells to doxorubicin","authors":"Lei Huang , Xiaobin Zeng , Kaimin Xiao , Sen Tang , Kuo Sun","doi":"10.1016/j.acthis.2025.152249","DOIUrl":"10.1016/j.acthis.2025.152249","url":null,"abstract":"<div><h3>Background</h3><div>Osteosarcoma is one of the most common malignant tumors in children and adolescents. It occurs in the metaphysis of long bones and is a type of aggressive malignant tumor. Although there are treatment methods such as surgery and chemotherapy, the mortality and disability of osteosarcoma patients are still high. With the emergence of more and more chemotherapy resistance, it is necessary to find new therapies to improve the chemotherapy sensitivity of osteosarcoma.</div></div><div><h3>Methods</h3><div>Drug-resistant MG-63 and U2OS cell strain was established in vitro by continuous exposure of human osteosarcoma cells to doxorubicin at gradually increasing concentrations,then determined for resistance index to doxorubicin by MTT method,for transcriptions of Livin mRNA by real-time polymerase chain reaction(RT⁃PCR),and for expressions of Livin proteins by Western blot.The technology of gene recombination was used to construct the eukaryotic expression vector pSilencer3.1-H1 neo-Livin. Then the pSilencer3.1-H1 neo-Livin was transfected into drug-resistant MG-63 cell by using Lipofectmine 2000. Expressions of Livin mRNA and protein in the transfected cells were respectively measured by RT-PCR and Western blot. The distribution of cell cycle phase and apoptosis were determined by flow cytometry. The analysis of chemotherapeutic sensitivity of drug-resistant MG-63 cell to doxorubicin was performed by MTT.</div></div><div><h3>Results</h3><div>The recombinant eukaryotic expression vector pSilencer3.1-H1 neo-Livin was successfully constructed. The result of inverted microscope revealed that the drug-resistant MG-63 cell were irregularity and morphological diversity. Compared with those in osteosarcoma cells,the transcription levels of Livin mRNA and protein in drug-resistant osteosarcoma cell increased(P<0.05).The flow cytometry analysis showed there was higher percentage of apoptosis in transfected drug-resistant MG-63 cell. Compared with control groups,the expression of Livin mRNA and protein were both significantly decreased in the transfected drug-resistant osteosarcomacell(P<0.05). We also observed that suppression of Livin expression in osteosarcoma cells increased their chemosensitivity to doxorubicin.</div></div><div><h3>Conclusion</h3><div>This study showed that Livin shRNA inhibited the proliferation level and increased the sensitivity of drug-resistant osteosarcoma cell to doxorubicin, suggested that Livin is involved in drug resistance of human osteosarcoma and may serve as a promising therapeutic target for osteosarcoma.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 2","pages":"Article 152249"},"PeriodicalIF":2.3,"publicationDate":"2025-03-22","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143683336","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta histochemicaPub Date : 2025-03-17DOI: 10.1016/j.acthis.2025.152247
Nikola Pavlović , Nela Kelam , Anita Racetin , Andrea Gelemanović , Natalija Filipović , Patricija Bajt , Yu Katsuyama , Katarina Vukojević
{"title":"The significance of Itga8 and Vangl2 in kidney development: Insights from yotari mice","authors":"Nikola Pavlović , Nela Kelam , Anita Racetin , Andrea Gelemanović , Natalija Filipović , Patricija Bajt , Yu Katsuyama , Katarina Vukojević","doi":"10.1016/j.acthis.2025.152247","DOIUrl":"10.1016/j.acthis.2025.152247","url":null,"abstract":"<div><div>The permanent kidney develops from the metanephros through the interaction of the ureteric bud (UB) and metanephric mesenchyme (MM). Congenital anomalies of the kidney and urinary tract (CAKUT) are common prenatal diagnoses, and genetic factors play a critical role in their development. This study explores the involvement of Integrin alpha-8 (Itga8) and Van Gogh-like 2 (Vangl2) proteins in kidney development, using the <em>yotari</em> (<em>yot</em>) mouse model, which harbors a mutation in the <em>Dab1</em> gene, disrupting Reelin signaling. Immunofluorescence was employed to analyze the spatiotemporal expression patterns of these proteins in embryonic and postnatal kidney samples. Our results show that Itga8 and Vangl2 expression is significantly higher in the embryonic kidneys of <em>yot</em> mice than those of wt mice. However, the two groups observed no significant differences in the temporal expression of these proteins in postnatal kidneys. Spatially, Itga8 was most strongly expressed in the metanephric mesenchyme and renal vesicles/immature glomeruli. At the same time, Vangl2 showed the highest expression in the metanephric mesenchyme, renal vesicles/immature glomeruli, and collecting ducts in <em>yot</em> mice. Our findings suggest that the <em>Dab1</em> mutation disrupts the expression of Itga8 and Vangl2, contributing to kidney developmental defects associated with CAKUT phenotypesThis increased expression suggests a disruption in the normal regulation of these proteins, likely due to the Dab1 mutation, which impairs Reelin signaling. Still, the exact mechanism through which the Reelin/Dab1 pathway influences the expression of examined markers remains to be elucidated. These results offer valuable insights into the factors associated with kidney malformations and suggest potential therapeutic targets for CAKUT abnormalities.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 2","pages":"Article 152247"},"PeriodicalIF":2.3,"publicationDate":"2025-03-17","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143642841","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta histochemicaPub Date : 2025-02-27DOI: 10.1016/j.acthis.2025.152237
KeerthiShri Boopathy , Thirunavukkarasu Palaniyandi , Maddaly Ravi , Mugip Rahaman Abdul Wahab , Gomathy Baskar , Safia Obaidur Rab , Mohd Saeed , Vishal M. Balaramnavar
{"title":"Exploring the potential of stem cell therapy: Applications, types, and future directions","authors":"KeerthiShri Boopathy , Thirunavukkarasu Palaniyandi , Maddaly Ravi , Mugip Rahaman Abdul Wahab , Gomathy Baskar , Safia Obaidur Rab , Mohd Saeed , Vishal M. Balaramnavar","doi":"10.1016/j.acthis.2025.152237","DOIUrl":"10.1016/j.acthis.2025.152237","url":null,"abstract":"<div><div>One of the most significant treatment approaches now accessible is stem cell therapy. Over the last few decades, a lot of study has been done in this field, and this fascinating feature of plasticity could have therapeutic uses. The potential of stem cells to restore function lost as a result of disease, trauma, congenital defects, and age has made stem cell research a key priority for scientific and medical organizations across the world. Stem cells are a crucial topic of study in regenerative medicine because of their capacity to replace, repair, or regenerate damaged cells, tissues, or organs. As a result, stem cell therapy is being used as a treatment strategy for a number of illnesses. Because stem cells may proliferate indefinitely and generate vast quantities of differentiated cells needed for transplantation, they hold enormous promise for regenerative medicine. Stem cells can be reprogrammed from adult cell types or originate from embryonic or fetal origins. Depending on their availability and place of origin, stem cells can be totipotent, pluripotent, multipotent, oligopotent, or unipotent. With stem cell treatment, many ailments, including diabetes, liver disease, infertility, wounds and traumas, neurological disorders, cardiovascular disease, and cancer, might be cured. Various types of stem cell treatment are described in this review along with their applications in different therapeutic fields, ethical considerations, and advantages and disadvantages.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 2","pages":"Article 152237"},"PeriodicalIF":2.3,"publicationDate":"2025-02-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143509520","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"EFNA1 promotes the tumorigenesis and metastasis of cervical cancer by phosphorylation pathway and epithelial-mesenchymal transition","authors":"Xiaorui Dong , Xixi Chen , Mengling Xue , Yina Zhang , Peiyue Jiang","doi":"10.1016/j.acthis.2025.152236","DOIUrl":"10.1016/j.acthis.2025.152236","url":null,"abstract":"<div><h3>Background</h3><div>Cervical cancer (CC) is a common gynecological disease that seriously threatens women’s health. This study aims to explore key genes and pathways related to CC prognosis through bioinformatics, providing new insights for further treatment of CC.</div></div><div><h3>Methods</h3><div>CC patient data were analyzed from the public databases. The enrichment analyses explored the roles and pathways of CC-related differentially expressed genes (DEGs). A prognostic key gene was identified using Venn diagrams and subjected to survival analysis. Gene Set Enrichment Analysis (GSEA) was employed to investigate the potential pathways of key genes. Correlations between the key gene and clinical features were examined. The function of the key gene was validated through immunohistochemistry, flow cytometry, transwell, MTT, and Western blot assays <em>in vitro</em> and <em>in vivo</em>.</div></div><div><h3>Results</h3><div>Our research identified 2459 upregulated genes among DEGs between healthy and tumor cervical tissues. These DEGs were primarily enriched in the PI3K-AKT and MAPK pathways. Moreover, EFNA1 was recognized as a key prognostic gene in CC, with elevated expression compared to normal tissue. A negative correlation between EFNA1 levels and patient survival rates was corroborated by Kaplan-Meier analysis. Furthermore, EFNA1 expression correlated with the cancer stage and was linked to antigen presentation, folate synthesis, and IL-17 signaling. Knockdown of EFNA1 enhanced apoptosis and reduced migration, invasion, and proliferation <em>in vitro</em> and <em>in vivo</em>, inhibiting EMT and MAPK pathways.</div></div><div><h3>Conclusion</h3><div>This study revealed the key signaling pathways in CC progression and identified EFNA1 as a crucial prognostic biomarker, potentially impacting CC treatment.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 2","pages":"Article 152236"},"PeriodicalIF":2.3,"publicationDate":"2025-02-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143474528","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Acta histochemicaPub Date : 2025-02-20DOI: 10.1016/j.acthis.2025.152238
Rafaela Marocci Lima Pimenta , Cara Skon-Hegg , Teresa Rose-Hellekant , Jon Holy
{"title":"Mechanoresponsive patterns of KLF2, 4, 5, and 6 expression differ among subclones from a single mammary tumor","authors":"Rafaela Marocci Lima Pimenta , Cara Skon-Hegg , Teresa Rose-Hellekant , Jon Holy","doi":"10.1016/j.acthis.2025.152238","DOIUrl":"10.1016/j.acthis.2025.152238","url":null,"abstract":"<div><div>A number of Krüppel-like transcription factor (KLF) family members display mechanoresponsive behaviors, and function as mechanosensitive transcription factors. There are many normal and pathological conditions where their roles in mechanotransduction and mechanoadaptation are not well understood, however. In this study, two basic questions regarding KLF mechanoresponsiveness were addressed: 1) are KLF 2, 4, 5, and 6 expressed at different levels among subclones of tumor cells adapted to specific microenvironmental conditions; and 2) is the expression of these KLFs responsive to rapid changes in the physical environment? To address these questions, the heterogeneous and differentially metastatic murine mammary tumor subclones 4T1, 4T07, and 67NR were subjected to physical changes in their culture conditions, and KLF responses assessed. The results show that the expression of different KLFs exhibit distinct responses to reductions in cell tension, as well as cell detachment from 2D and 3D environments. KLF2 and 4 expression is rapidly and temporarily induced upon release of cells from a stiff 2D substrate into liquid suspension culture in all three subclones, and similar responses are observed in two of the subclones upon the release of tension in 3D collagen gel cultures. By contrast, expression patterns of KLF5 and 6 were generally less affected by physical changes in most, but not all, of the cell lines examined. These results support the concept that KLFs differentially participate in transducing physical differences among intratumoral neighborhoods into distinct responses among heterogeneous subclones, thereby contributing to tumor cell behavioral complexity.</div></div>","PeriodicalId":6961,"journal":{"name":"Acta histochemica","volume":"127 2","pages":"Article 152238"},"PeriodicalIF":2.3,"publicationDate":"2025-02-20","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"143464519","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":4,"RegionCategory":"生物学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}