Cargando…

Oncological transformation in vitro of hepatic progenitor cell lines isolated from adult mice

Colorectal cancer cells can transfer the oncogene KRAS to distant cells, predisposing them to malignant transformation (Genometastasis Theory). This process could contribute to liver metastasis; besides, hepatic progenitor cells (HPCs) have been found to be involved in liver malignant neoplasms. The...

Descripción completa

Detalles Bibliográficos
Autores principales: Olivera-Salazar, Rocío, García-Arranz, Mariano, Sánchez, Aránzazu, Olmedillas-López, Susana, Vega-Clemente, Luz, Serrano, Luis Javier, Herrera, Blanca, García-Olmo, Damián
Formato: Online Artículo Texto
Lenguaje:English
Publicado: Nature Publishing Group UK 2022
Materias:
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8873244/
https://www.ncbi.nlm.nih.gov/pubmed/35210455
http://dx.doi.org/10.1038/s41598-022-06427-w
_version_ 1784657422244118528
author Olivera-Salazar, Rocío
García-Arranz, Mariano
Sánchez, Aránzazu
Olmedillas-López, Susana
Vega-Clemente, Luz
Serrano, Luis Javier
Herrera, Blanca
García-Olmo, Damián
author_facet Olivera-Salazar, Rocío
García-Arranz, Mariano
Sánchez, Aránzazu
Olmedillas-López, Susana
Vega-Clemente, Luz
Serrano, Luis Javier
Herrera, Blanca
García-Olmo, Damián
author_sort Olivera-Salazar, Rocío
collection PubMed
description Colorectal cancer cells can transfer the oncogene KRAS to distant cells, predisposing them to malignant transformation (Genometastasis Theory). This process could contribute to liver metastasis; besides, hepatic progenitor cells (HPCs) have been found to be involved in liver malignant neoplasms. The objective of this study is to determine if mouse HPCs—Oval cells (OCs)—are susceptible to incorporate Kras GAT (G12D) mutation from mouse colorectal cancer cell line CT26.WT and if OCs with the incorporated mutation behave like malignant cells. To achieve this, three lines of OCs in different conditions were exposed to CT26.WT cells through transwell co-culture for a week. The presence of Kras(G12D) and capacity to form tumors were analyzed in treated samples by droplet digital PCR and colony-forming assays, respectively. The results showed that the Kras(G12D) mutation was detected in hepatic culture conditions of undifferentiated OCs and these cells were capable of forming tumors in vitro. Therefore, OCs are susceptible to malignant transformation by horizontal transfer of DNA with Kras(G12D) mutation in an undifferentiated condition associated with the liver microenvironment. This study contributes to a new step in the understanding of the colorectal metastatic process.
format Online
Article
Text
id pubmed-8873244
institution National Center for Biotechnology Information
language English
publishDate 2022
publisher Nature Publishing Group UK
record_format MEDLINE/PubMed
spelling pubmed-88732442022-02-25 Oncological transformation in vitro of hepatic progenitor cell lines isolated from adult mice Olivera-Salazar, Rocío García-Arranz, Mariano Sánchez, Aránzazu Olmedillas-López, Susana Vega-Clemente, Luz Serrano, Luis Javier Herrera, Blanca García-Olmo, Damián Sci Rep Article Colorectal cancer cells can transfer the oncogene KRAS to distant cells, predisposing them to malignant transformation (Genometastasis Theory). This process could contribute to liver metastasis; besides, hepatic progenitor cells (HPCs) have been found to be involved in liver malignant neoplasms. The objective of this study is to determine if mouse HPCs—Oval cells (OCs)—are susceptible to incorporate Kras GAT (G12D) mutation from mouse colorectal cancer cell line CT26.WT and if OCs with the incorporated mutation behave like malignant cells. To achieve this, three lines of OCs in different conditions were exposed to CT26.WT cells through transwell co-culture for a week. The presence of Kras(G12D) and capacity to form tumors were analyzed in treated samples by droplet digital PCR and colony-forming assays, respectively. The results showed that the Kras(G12D) mutation was detected in hepatic culture conditions of undifferentiated OCs and these cells were capable of forming tumors in vitro. Therefore, OCs are susceptible to malignant transformation by horizontal transfer of DNA with Kras(G12D) mutation in an undifferentiated condition associated with the liver microenvironment. This study contributes to a new step in the understanding of the colorectal metastatic process. Nature Publishing Group UK 2022-02-24 /pmc/articles/PMC8873244/ /pubmed/35210455 http://dx.doi.org/10.1038/s41598-022-06427-w Text en © The Author(s) 2022 https://creativecommons.org/licenses/by/4.0/Open Access This article is licensed under a Creative Commons Attribution 4.0 International License, which permits use, sharing, adaptation, distribution and reproduction in any medium or format, as long as you give appropriate credit to the original author(s) and the source, provide a link to the Creative Commons licence, and indicate if changes were made. The images or other third party material in this article are included in the article's Creative Commons licence, unless indicated otherwise in a credit line to the material. If material is not included in the article's Creative Commons licence and your intended use is not permitted by statutory regulation or exceeds the permitted use, you will need to obtain permission directly from the copyright holder. To view a copy of this licence, visit http://creativecommons.org/licenses/by/4.0/ (https://creativecommons.org/licenses/by/4.0/) .
spellingShingle Article
Olivera-Salazar, Rocío
García-Arranz, Mariano
Sánchez, Aránzazu
Olmedillas-López, Susana
Vega-Clemente, Luz
Serrano, Luis Javier
Herrera, Blanca
García-Olmo, Damián
Oncological transformation in vitro of hepatic progenitor cell lines isolated from adult mice
title Oncological transformation in vitro of hepatic progenitor cell lines isolated from adult mice
title_full Oncological transformation in vitro of hepatic progenitor cell lines isolated from adult mice
title_fullStr Oncological transformation in vitro of hepatic progenitor cell lines isolated from adult mice
title_full_unstemmed Oncological transformation in vitro of hepatic progenitor cell lines isolated from adult mice
title_short Oncological transformation in vitro of hepatic progenitor cell lines isolated from adult mice
title_sort oncological transformation in vitro of hepatic progenitor cell lines isolated from adult mice
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8873244/
https://www.ncbi.nlm.nih.gov/pubmed/35210455
http://dx.doi.org/10.1038/s41598-022-06427-w
work_keys_str_mv AT oliverasalazarrocio oncologicaltransformationinvitroofhepaticprogenitorcelllinesisolatedfromadultmice
AT garciaarranzmariano oncologicaltransformationinvitroofhepaticprogenitorcelllinesisolatedfromadultmice
AT sanchezaranzazu oncologicaltransformationinvitroofhepaticprogenitorcelllinesisolatedfromadultmice
AT olmedillaslopezsusana oncologicaltransformationinvitroofhepaticprogenitorcelllinesisolatedfromadultmice
AT vegaclementeluz oncologicaltransformationinvitroofhepaticprogenitorcelllinesisolatedfromadultmice
AT serranoluisjavier oncologicaltransformationinvitroofhepaticprogenitorcelllinesisolatedfromadultmice
AT herrerablanca oncologicaltransformationinvitroofhepaticprogenitorcelllinesisolatedfromadultmice
AT garciaolmodamian oncologicaltransformationinvitroofhepaticprogenitorcelllinesisolatedfromadultmice