Abstract
BackgroundCancer stem cells (CSCs) are generated under irregular microenvironment in vivo, of which mimic is quite difficult due to the lack of enough information of the factors responsible for cancer initiation. Here, we demonstrated that mouse induced pluripotent cells (miPSCs) reprogrammed from normal embryonic fibroblasts were susceptible to the microenvironment affected by cancer cells to convert into CSCs in vivo.MethodsThree different pancreatic cancer line cells, BxPC3, PANC1, and PK8 cells were mixed with miPSCs and subcutaneously injected into immunodeficient mice. Tumors were evaluated by histological analysis and cells derived from iPSCs were isolated and selected from tumors. The isolated cells were characterized for cancer stem cell characters in vitro and in vivo as well as their responses to anticancer drugs. The impact of co-injection of iPSCs with cancer cells on transcriptome and signaling pathways of iPSCs was investigated.ResultsThe injection of miPSCs mixed with human pancreatic cancer cells into immunodeficient mice maintained the stemness of miPSCs and changed their phenotype. The miPSCs acquired CSC characteristics of tumorigenicity and self-renewal. The drug responses and the metastatic ability of CSCs converted from miPSCs varied depending on the microenvironment of cancer cells. Interestingly, transcriptome profiles of these cells indicated that the pathways related with aggressiveness and energy production were upregulated from the levels of miPSCs.ConclusionsOur result suggests that cancer-inducing microenvironment in vivo could rewire the cell signaling and metabolic pathways to convert normal stem cells into CSCs.
Highlights
Cancer stem cells (CSCs) are generated under irregular microenvironment in vivo, of which mimic is quite difficult due to the lack of enough information of the factors responsible for cancer initiation
For the primary culture of cells from tumors, tumor tissues were washed with phosphate-buffered saline (PBS), finely minced with a razor blade in Hank’s balanced salt solution (HBSS) and 1 ml of tissue suspension was transferred into 15-ml tubes containing 1 ml of dissociation buffer consisting of 0.1% collagenase, 0.25% trypsin, 20% KnockOut Serum Replacement (Thermo Fischer Scientific, MA), and 1 mM of CaCl2 (Sigma-Aldrich, MO) in PBS
The Induced pluripotent stem cells (iPSCs) survived in the tumors by the co‐injection with cancer cells The origin of CSCs could be hypothesized normal stem cells
Summary
Cancer stem cells (CSCs) are generated under irregular microenvironment in vivo, of which mimic is quite difficult due to the lack of enough information of the factors responsible for cancer initiation. We demonstrated that mouse induced pluripotent cells (miPSCs) reprogrammed from normal embryonic fibroblasts were susceptible to the microenvironment affected by cancer cells to convert into CSCs in vivo. Hassan et al J Exp Clin Cancer Res (2022) 41:29 cells and fibroblasts. Upon various stimuli, these cells produce factors such as proteases, growth factors, and chemokines which play essential roles in the growth and survival of cancer cells [2, 3]. The chronic inflammatory microenvironment, disrupting tissue homeostasis for a long period, creates a tumor inducing niche. Since the cellular and biochemical processes involved in wound healing share a good similarity with those in the growth and development of tumors, a tumor is often described as “a wound that does not heal” [5]
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