دورية أكاديمية
أعرض في EDS

A new aggressive xenograft model of human colon cancer using cancer-associated fibroblasts.

التفاصيل البيبلوغرافية
العنوان: A new aggressive xenograft model of human colon cancer using cancer-associated fibroblasts.
المؤلفون: Fernando-Macías E; Service of Surgery, Hospital Universitario Central de Asturias, Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain., Fernández-García MT; Laboratory of Department of Molecular Histopathology in Animal Cancer Models, Oncology University Institute of the Principality of Asturias, University of Oviedo, Oviedo, Spain., García-Pérez E; Ophtalmologic Research Foundation, Oviedo, Spain., Porrero Guerrero B; Service of Surgery, Hospital Universitario Central de Asturias, Oviedo, Spain., López-Arévalo C; Service of Surgery, Hospital Universitario Central de Asturias, Oviedo, Spain., Rodríguez-Uría R; Service of Surgery, Hospital Universitario Central de Asturias, Oviedo, Spain., Sanz-Navarro S; Service of Surgery, Hospital Universitario Central de Asturias, Oviedo, Spain., Vázquez-Villa JF; Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain., Muñíz-Salgueiro MC; Laboratory of Department of Molecular Histopathology in Animal Cancer Models, Oncology University Institute of the Principality of Asturias, University of Oviedo, Oviedo, Spain., Suárez-Fernández L; Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain., Galván JA; Translational Research Unit, Institute of Pathology, University of Bern, Bern, Switzerland., Barneo-Caragol C; Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain.; Laboratory of Medicine, Department of Clinical Biochemistry, Hospital Universitario Central de Asturias, Oviedo, Spain., García-Ocaña M; Biotechnological and Biomedical Assays Unit, Technical-Scientific Services, University of Oviedo, Oviedo, Spain., de Los Toyos JR; Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain.; Immunology Department, School of Medicine and Health Sciences, University of Oviedo, Oviedo, Spain., Barneo-Serra L; Service of Surgery, Hospital Universitario Central de Asturias, Oviedo, Spain.; Instituto de Investigación Sanitaria del Principado de Asturias, Oviedo, Spain.; Surgery Department, School of Medicine and Health Sciences, University of Oviedo, Oviedo, Spain.
المصدر: PeerJ [PeerJ] 2020 Jun 03; Vol. 8, pp. e9045. Date of Electronic Publication: 2020 Jun 03 (Print Publication: 2020).
نوع المنشور: Journal Article
اللغة: English
بيانات الدورية: Publisher: PeerJ Inc Country of Publication: United States NLM ID: 101603425 Publication Model: eCollection Cited Medium: Print ISSN: 2167-8359 (Print) Linking ISSN: 21678359 NLM ISO Abbreviation: PeerJ Subsets: PubMed not MEDLINE
أسماء مطبوعة: Original Publication: Corte Madera, CA : PeerJ Inc.
مستخلص: Background: Colorectal cancer is the second leading cause of cancer death. Almost half of the patients present recurrence within 5 years after the treatment of the primary tumor, the majority, with metastasis. On the other hand, in the search for new animal models that simulate metastatic cancer, it has been suggested that fibroblasts immersed in the peritumoral stroma (cancer-associated fibroblasts (CAFs)), play a relevant role in the development of cancer. The objective of this study was to identify an adequate animal model to study metastatic colon cancer and the application of new treatments.
Methods: Human CAFs and normal fibroblasts (NF) for transplant and culture were obtained from surgical fresh samples of patients with adenocarcinoma of sigmoid colon. Stromal cell purity was evaluated by morphology and immunostaining with vimentin (VIM) as a fibroblast marker and anti-proColXIα1 as a specific human CAF marker. Phenotypic characterization of cultured stromal cells was performed by co-staining with mesenchymal and epithelial cell markers. For identification in mice, human CAFs were labeled with the PKH26 red fluorescence dye. Cell line HT-29 was used as tumor cells. Transplant in the head of the pancreas of 34 SCID mice was performed in four different groups, as follows: I. 150,000 CAFS ( n = 12), IIa. 1.5 million HT29 cells ( n = 7), IIb. 150,000 NF+1.5 million HT29 cells ( n = 5), III. 150,000 CAFS+1.5 million HT29 cells ( n = 10). After euthanasia performed one month later, histological analysis was made using hematoxylin-eosin and anti-proColXIα1. A histopathological score system based on three features (tumor volume, desmoplasia and number of metastasized organs) was established to compare the tumor severity.
Results: The CAFs and NF cultured were proColXIα1+/VIM+, proColXIα1/alphaSMA+ and proColXIα1+/CK19+ in different proportions without differences among them, but the CAFs growth curve was significantly larger than that of the NF ( p < 0.05). No tumor developed in those animals that only received CAFs. When comparing group II (a + b) vs. group III, both groups showed 100% hepatic metastases. Median hepatic nodules, tumor burden, lung metastases and severity score were bigger in group III vs group II (a + b), although without being significant, except in the case of the median tumor volume, that was significantly higher in group III (154.8 (76.9-563.2) mm 3 ) vs group II (46.7 (3.7-239.6) mm 3 ), p = 0.04. A correlation was observed between the size of the tumor developed in the pancreas and the metastatic tumor burden in the liver and with the severity score.
Conclusion: Our experiments demonstrate that cultured CAFs have a higher growth than NF and that when human CAFs are associated to human tumor cells, larger tumors with liver and lung metastases are generated than if only colon cancer cells with/without NF are transplanted. This emphasizes the importance of the tumor stroma, and especially the CAFs, in the development of cancer.
Competing Interests: The proCOL11A1 mAb has been patented by Oncomatryx, S.L (PCT/ES2012/070616; WO 2013/021088 A2).
(© 2020 Fernando-Macías et al.)
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فهرسة مساهمة: Keywords: Animal model; CAFs; Fibroblasts culture; ProColXIα1; Xenograft
تواريخ الأحداث: Date Created: 20200618 Latest Revision: 20220415
رمز التحديث: 20221213
مُعرف محوري في PubMed: PMC7275677
DOI: 10.7717/peerj.9045
PMID: 32547853
قاعدة البيانات: MEDLINE
الوصف
تدمد:2167-8359
DOI:10.7717/peerj.9045