Abstract

Cancer stem cells (CSCs) subpopulation within the tumour is responsible for metastasis and cancer relapse. Here we investigate in vitro and in vivo the effects of a pancreatic (pro)enzyme mixture composed of Chymotrypsinogen and Trypsinogen (PRP) on CSCs derived from a human pancreatic cell line, BxPC3. Exposure of pancreatic CSCs spheres to PRP resulted in a significant decrease of ALDEFLUOR and specific pancreatic CSC markers (CD 326, CD 44 and CxCR4) signal tested by flow cytometry, further CSCs markers expression was also analyzed by western and immunofluorescence assays. PRP also inhibits primary and secondary sphere formation. Three RT2 Profiler PCR Arrays were used to study gene expression regulation after PRP treatment and resulted in, (i) epithelial-mesenchymal transition (EMT) inhibition; (ii) CSCs related genes suppression; (iii) enhanced expression of tumour suppressor genes; (iv) downregulation of migration and metastasis genes and (v) regulation of MAP Kinase Signalling Pathway. Finally, in vivo anti-tumor xenograft studies demonstrated high anti-tumour efficacy of PRP against tumours induced by BxPC3 human pancreatic CSCs. PRP impaired engrafting of pancreatic CSC’s tumours in nude mice and displayed an antigrowth effect toward initiated xenografts. We concluded that (pro)enzymes treatment is a valuable strategy to suppress the CSC population in solid pancreatic tumours.

Details

Title
Pancreatic (pro)enzymes treatment suppresses BXPC-3 pancreatic Cancer Stem Cell subpopulation and impairs tumour engrafting
Author
Hernández-Camarero, Pablo 1 ; López-Ruiz, Elena 2 ; Griñán-Lisón, Carmen 3 ; García, María Ángel 4 ; Chocarro-Wrona, Carlos 3 ; Marchal, Juan Antonio 3   VIAFID ORCID Logo  ; Kenyon, Julian 5 ; Perán, Macarena 1   VIAFID ORCID Logo 

1  Department of Health Sciences, University of Jaén, Jaén, Spain; Excellence Research Unit “Modeling Nature” (MNat), University of Granada, Granada, Spain 
2  Department of Health Sciences, University of Jaén, Jaén, Spain; Biopathology and Regenerative Medicine, Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, Granada, Spain; Biosanitary Research Institute of Granada (ibs. GRANADA), University Hospitals of Granada-University of Granada, Granada, Spain; Excellence Research Unit “Modeling Nature” (MNat), University of Granada, Granada, Spain 
3  Biopathology and Regenerative Medicine, Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, Granada, Spain; Biosanitary Research Institute of Granada (ibs. GRANADA), University Hospitals of Granada-University of Granada, Granada, Spain; Department of Human Anatomy and Embryology, Faculty of Medicine, University of Granada, Granada, Spain; Excellence Research Unit “Modeling Nature” (MNat), University of Granada, Granada, Spain 
4  Biopathology and Regenerative Medicine, Institute (IBIMER), Centre for Biomedical Research (CIBM), University of Granada, Granada, Spain; Biosanitary Research Institute of Granada (ibs. GRANADA), University Hospitals of Granada-University of Granada, Granada, Spain; Department of Biochemistry and Molecular Biology 3 and Immunology, University of Granada, Granada, Spain; Excellence Research Unit “Modeling Nature” (MNat), University of Granada, Granada, Spain 
5  The Dove Clinic for Integrated Medicine, Twyford, UK 
Pages
1-17
Publication year
2019
Publication date
Aug 2019
Publisher
Nature Publishing Group
e-ISSN
20452322
Source type
Scholarly Journal
Language of publication
English
DOI
https://doi.org/10.1038/s41598-019-47837-7
ProQuest document ID
2268792213
Copyright
© 2019. This work is published under http://creativecommons.org/licenses/by/4.0/ (the “License”). Notwithstanding the ProQuest Terms and Conditions, you may use this content in accordance with the terms of the License.