Pancreatic (pro)enzymes treatment suppresses BXPC-3 pancreatic Cancer Stem Cell subpopulation and impairs tumour engrafting
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...
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doaj-24983c8908a44af1b34f202750f310692020-12-08T07:10:10ZengNature Publishing GroupScientific Reports2045-23222019-08-019111710.1038/s41598-019-47837-7Pancreatic (pro)enzymes treatment suppresses BXPC-3 pancreatic Cancer Stem Cell subpopulation and impairs tumour engraftingPablo Hernández-Camarero0Elena López-Ruiz1Carmen Griñán-Lisón2María Ángel García3Carlos Chocarro-Wrona4Juan Antonio Marchal5Julian Kenyon6Macarena Perán7Department of Health Sciences, University of JaénDepartment of Health Sciences, University of JaénBiopathology and Regenerative Medicine, Institute (IBIMER), Centre for Biomedical Research (CIBM), University of GranadaBiopathology and Regenerative Medicine, Institute (IBIMER), Centre for Biomedical Research (CIBM), University of GranadaBiopathology and Regenerative Medicine, Institute (IBIMER), Centre for Biomedical Research (CIBM), University of GranadaBiopathology and Regenerative Medicine, Institute (IBIMER), Centre for Biomedical Research (CIBM), University of GranadaThe Dove Clinic for Integrated MedicineDepartment of Health Sciences, University of JaénAbstract 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.https://doi.org/10.1038/s41598-019-47837-7 |
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DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Pablo Hernández-Camarero Elena López-Ruiz Carmen Griñán-Lisón María Ángel García Carlos Chocarro-Wrona Juan Antonio Marchal Julian Kenyon Macarena Perán |
spellingShingle |
Pablo Hernández-Camarero Elena López-Ruiz Carmen Griñán-Lisón María Ángel García Carlos Chocarro-Wrona Juan Antonio Marchal Julian Kenyon Macarena Perán Pancreatic (pro)enzymes treatment suppresses BXPC-3 pancreatic Cancer Stem Cell subpopulation and impairs tumour engrafting Scientific Reports |
author_facet |
Pablo Hernández-Camarero Elena López-Ruiz Carmen Griñán-Lisón María Ángel García Carlos Chocarro-Wrona Juan Antonio Marchal Julian Kenyon Macarena Perán |
author_sort |
Pablo Hernández-Camarero |
title |
Pancreatic (pro)enzymes treatment suppresses BXPC-3 pancreatic Cancer Stem Cell subpopulation and impairs tumour engrafting |
title_short |
Pancreatic (pro)enzymes treatment suppresses BXPC-3 pancreatic Cancer Stem Cell subpopulation and impairs tumour engrafting |
title_full |
Pancreatic (pro)enzymes treatment suppresses BXPC-3 pancreatic Cancer Stem Cell subpopulation and impairs tumour engrafting |
title_fullStr |
Pancreatic (pro)enzymes treatment suppresses BXPC-3 pancreatic Cancer Stem Cell subpopulation and impairs tumour engrafting |
title_full_unstemmed |
Pancreatic (pro)enzymes treatment suppresses BXPC-3 pancreatic Cancer Stem Cell subpopulation and impairs tumour engrafting |
title_sort |
pancreatic (pro)enzymes treatment suppresses bxpc-3 pancreatic cancer stem cell subpopulation and impairs tumour engrafting |
publisher |
Nature Publishing Group |
series |
Scientific Reports |
issn |
2045-2322 |
publishDate |
2019-08-01 |
description |
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. |
url |
https://doi.org/10.1038/s41598-019-47837-7 |
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