RT Journal Article
T1 Pancreatic (pro)enzymes treatment suppresses BXPC-3 pancreatic Cancer Stem Cell subpopulation and impairs tumour engrafting.
A1 Hernandez-Camarero, Pablo
A1 Lopez-Ruiz, Elena
A1 Griñan-Lison, Carmen
A1 Garcia, Maria Angel
A1 Chocarro-Wrona, Carlos
A1 Marchal, Juan Antonio
A1 Kenyon, Julian
A1 Peran, Macarena
K1 Drug development
K1 Cancer stem cells
K1 Chymotrypsinogen
K1 Genes, Tumor Suppressor
K1 Mice, Nude
AB 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.
PB Nature Publishing Group
YR 2019
FD 2019-07-23
LK http://hdl.handle.net/10668/14370
UL http://hdl.handle.net/10668/14370
LA en
NO 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.
DS RISalud
RD Apr 12, 2025