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Home / Equine Research Bank / Int J Mol Sci / Tracking the Molecular Scenarios for Tumorigenic Remodeling ...
International journal of molecular sciences2022; 23(12); 6506; doi: 10.3390/ijms23126506

Tracking the Molecular Scenarios for Tumorigenic Remodeling of Extracellular Matrix Based on Gene Expression Profiling in Equine Skin Neoplasia Models.

Abstract: An important component of tissues is the extracellular matrix (ECM), which not only forms a tissue scaffold, but also provides the environment for numerous biochemical reactions. Its composition is strictly regulated, and any irregularities can result in the development of many diseases, including cancer. Sarcoid is the most common skin cancer in equids. Its formation results from the presence of the genetic material of the bovine papillomavirus (BPV). In addition, it is assumed that sarcoid-dependent oncogenic transformation arises from a disturbed wound healing process, which may be due to the incorrect functioning of the ECM. Moreover, sarcoid is characterized by a failure to metastasize. Therefore, in this study we decided to investigate the differences in the expression profiles of genes related not only to ECM remodeling, but also to the cell adhesion pathway, in order to estimate the influence of disturbances within the ECM on the sarcoid formation process. Furthermore, we conducted comparative research not only between equine sarcoid tissue bioptates and healthy skin-derived explants, but also between dermal fibroblast cell lines transfected and non-transfected with a construct encoding the E4 protein of the BP virus, in order to determine its effect on ECM disorders. The obtained results strongly support the hypothesis that ECM-related genes are correlated with sarcoid formation. The deregulated expression of selected genes was shown in both equine sarcoid tissue bioptates and adult cutaneous fibroblast cell (ACFC) lines neoplastically transformed by nucleofection with gene constructs encoding BPV1-E1^E4 protein. The identified genes (, , and ) were up- or down-regulated, which pinpointed the phenotypic differences from the backgrounds noticed for adequate expression profiles in other cancerous or noncancerous tumors as reported in the available literature data. Unravelling the molecular pathways of ECM remodeling and cell adhesion in the in vivo and ex vivo models of epidermal/dermal sarcoid-related cancerogenesis might provide powerful tools for further investigations of genetic and epigenetic biomarkers for both silencing and re-initiating the processes of sarcoid-dependent neoplasia. Recognizing those biomarkers might insightfully explain the relatively high capacity of sarcoid-descended cancerous cell derivatives to epigenomically reprogram their nonmalignant neoplastic status in domestic horse cloned embryos produced by somatic cell nuclear transfer (SCNT).
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Publication Date: 2022-06-10 PubMed ID: 35742950PubMed Central: PMC9223705DOI: 10.3390/ijms23126506Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research article focuses on understanding the molecular changes in the extracellular matrix that contribute to the development of sarcoid, a common skin cancer in horses, with the aim of identifying possible genetic and epigenetic biomarkers for this disease.

Background and Aim

  • The extracellular matrix (ECM) is an integral part of tissues, contributing not just to its structure but also facilitating various biochemical processes. Any changes or ‘disturbances’ in its normal functioning can lead to diseases, including cancer.
  • Sarcoid is the most prevalent skin cancer found in equids, or horses. The cause of this cancer is believed to be the presence of genetic material from bovine papillomavirus (BPV).
  • The researchers aimed to study the alterations in gene expression related to the ECM’s function and cell adhesion, and how these disturbances might contribute to sarcoid formation.

Methodology

  • The researchers conducted comparative studies using tissue samples from equine sarcoid and healthy horse skin.
  • They also compared dermal fibroblast cell lines that were either transfected (expressing BP virus protein) and non-transfected to discern the impact of the BPV on ECM function.

Findings

  • The study found strong evidence supporting the hypothesis that discrepancies in ECM-related genes contribute significantly to the formation of sarcoid.
  • Genes such as COL1A1 CHI3L1, ADAMTS1, THBS2 and LOX were found to be deregulated in both equine sarcoid tissues and transfected fibroblast cells, suggesting these genes’ critical role in the onset of sarcoid.

Implications

  • This research helps unravel the molecular pathways involved in the remodeling of ECM and alterations in cell adhesion, contributing to sarcoid development in horses.
  • Understanding these processes could lead to the identification of genetic and epigenetic biomarkers that can potentially aid in better diagnosis and treatment of sarcoid.
  • Such biomarkers could help explain why sarcoid cells have a high capacity to epigenetically modify and maintain a non-malignant status in cloned horse embryos produced through somatic cell nuclear transfer.

Cite This Article

APA
Podstawski P, Ropka-Molik K, Semik-Gurgul E, Samiec M, Skrzyszowska M, Podstawski Z, Szmatoła T, Witkowski M, Pawlina-Tyszko K. (2022). Tracking the Molecular Scenarios for Tumorigenic Remodeling of Extracellular Matrix Based on Gene Expression Profiling in Equine Skin Neoplasia Models. Int J Mol Sci, 23(12), 6506. https://doi.org/10.3390/ijms23126506

Publication

International journal of molecular sciences
ISSN: 1422-0067
NlmUniqueID: 101092791
Country: Switzerland
Language: English
Volume: 23
Issue: 12
PII: 6506

Researcher Affiliations

Podstawski, Przemysław
  • Department of Animal Molecular Biology, National Research Institute of Animal Production, Krakowska 1 Street, Balice, 32-083 Kraków, Poland.
  • Department of Animal Reproduction, Anatomy and Genomics, University of Agriculture in Kraków, Mickiewicza 24/28, 30-059 Kraków, Poland.
Ropka-Molik, Katarzyna
  • Department of Animal Molecular Biology, National Research Institute of Animal Production, Krakowska 1 Street, Balice, 32-083 Kraków, Poland.
Semik-Gurgul, Ewelina
  • Department of Animal Molecular Biology, National Research Institute of Animal Production, Krakowska 1 Street, Balice, 32-083 Kraków, Poland.
Samiec, Marcin
  • Department of Reproductive Biotechnology and Cryoconservation, National Research Institute of Animal Production, Krakowska 1 Street, Balice, 32-083 Kraków, Poland.
Skrzyszowska, Maria
  • Department of Reproductive Biotechnology and Cryoconservation, National Research Institute of Animal Production, Krakowska 1 Street, Balice, 32-083 Kraków, Poland.
Podstawski, Zenon
  • Department of Animal Reproduction, Anatomy and Genomics, University of Agriculture in Kraków, Mickiewicza 24/28, 30-059 Kraków, Poland.
Szmatoła, Tomasz
  • Department of Animal Molecular Biology, National Research Institute of Animal Production, Krakowska 1 Street, Balice, 32-083 Kraków, Poland.
  • Center for Experimental and Innovative Medicine, University of Agriculture in Krakow, Rędzina 1c Street, 30-248 Kraków, Poland.
Witkowski, Maciej
  • Institute of Veterinary Medicine, University Centre of Veterinary Medicine JU-AU, Mickiewicza 24/28, 30-059 Kraków, Poland.
  • Horse Clinic Służewiec, Puławska 266 Street, 02-684 Warsaw, Poland.
Pawlina-Tyszko, Klaudia
  • Department of Animal Molecular Biology, National Research Institute of Animal Production, Krakowska 1 Street, Balice, 32-083 Kraków, Poland.

MeSH Terms

  • Animals
  • Bovine papillomavirus 1 / genetics
  • Cell Transformation, Neoplastic
  • Extracellular Matrix / metabolism
  • Gene Expression Profiling
  • Horse Diseases / metabolism
  • Horses / genetics
  • Papillomavirus Infections
  • Sarcoidosis
  • Skin Diseases
  • Skin Neoplasms / genetics
  • Skin Neoplasms / metabolism
  • Skin Neoplasms / veterinary

Grant Funding

  • DI2016 012746 / Ministry of Science and Higher Education
  • 04-19-11-21 / National Research Institute of Animal Production

Conflict of Interest Statement

The authors declare no conflict of interest. The funders had no role in the design of the study; in the collection, analyses, or interpretation of data; in the writing of the manuscript, or in the decision to publish the results.

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Citations

This article has been cited 1 times.
  1. Semik-Gurgul E, Gurgul A, Szmatoła T. Transcriptome and methylome sequencing reveals altered long non-coding RNA genes expression and their aberrant DNA methylation in equine sarcoids. Funct Integr Genomics 2023 Aug 8;23(3):268.
    doi: 10.1007/s10142-023-01200-2pubmed: 37552338google scholar: lookup
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