Publication:
Pancreatic (pro)enzymes treatment suppresses BXPC-3 pancreatic Cancer Stem Cell subpopulation and impairs tumour engrafting.

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Date

2019-07-23

Authors

Hernandez-Camarero, Pablo
Lopez-Ruiz, Elena
Griñan-Lison, Carmen
Garcia, Maria Angel
Chocarro-Wrona, Carlos
Marchal, Juan Antonio
Kenyon, Julian
Peran, Macarena

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Nature Publishing Group
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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.

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MeSH Terms

Animals
Cell Line, Tumor
Epithelial-Mesenchymal Transition
Gene Expression Regulation, Neoplastic
Humans
MAP Kinase Signaling System
Mice
Neoplastic Stem Cells
Pancreatic Neoplasms
Trypsinogen
Xenograft Model Antitumor Assays

DeCS Terms

Animales
Células madre Neoplásicas
Ensayos antitumor por modelo de xenoinjerto
Humanos
Línea celular tumoral
Neoplasias pancreáticas
Ratones
Regulación neoplásica de la expresión génica
Sistema de señalización de MAP Quinasas
Transición epitelial-mesenquimal
Tripsinógeno

CIE Terms

Keywords

Drug development, Cancer stem cells, Chymotrypsinogen, Genes, Tumor Suppressor, Mice, Nude

Citation

Hernández-Camarero P, López-Ruiz E, Griñán-Lisón C, García MÁ, Chocarro-Wrona C, Marchal JA, et al. Pancreatic (pro)enzymes treatment suppresses BXPC-3 pancreatic Cancer Stem Cell subpopulation and impairs tumour engrafting. Sci Rep. 2019 Aug 6;9(1):11359.