Stroma-directed imatinib therapy impairs the tumor-promoting effect of bone marrow-derived mesenchymal stem cells in an orthotopic transplantation model of colon cancer

2012 ◽  
Vol 132 (4) ◽  
pp. 813-823 ◽  
Author(s):  
Kei Shinagawa ◽  
Yasuhiko Kitadai ◽  
Miwako Tanaka ◽  
Tomonori Sumida ◽  
Mieko Onoyama ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Colon Cancer ◽  
Mesenchymal Stem Cells ◽  
Imatinib Therapy ◽  
Promoting Effect ◽  
Orthotopic Transplantation ◽  
Transplantation Model ◽  
Orthotopic Transplantation Model

scholarly journals Mesenchymal stem cells maintain the stemness of colon cancer stem cells via interleukin-8/mitogen-activated protein kinase signaling pathway

2020 ◽  
Vol 245 (6) ◽  
pp. 562-575
Author(s):  
Xiaoying Ma ◽  
Jiajun Liu ◽  
Xiaotong Yang ◽  
Kai Fang ◽  
Peiyong Zheng ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Colon Cancer ◽  
Mesenchymal Stem Cells ◽  
Signaling Pathway ◽  
Theoretical Basis ◽  
Mapk Signaling ◽  
Mitogen Activated Protein Kinase ◽  
Mitogen Activated Protein

Mesenchymal stem cells (MSCs) can act as a carrier in tumor therapy, and tumor suppressor gene-modified MSCs can reach and suppress the tumor. However, in the colon cancer microenvironment, MSCs could promote tumor growth and create the environment that is conducive to the survival of cancer stem cells (CSCs). This study discovered MSCs from three sources (bone marrow, adipose, placenta) could induce the stemness and epithelial–mesenchymal transition (EMT) of HCT116 in vitro, meanwhile adipose- and placenta-derived MSCs increase the proportion of CD133+/CD44+ HCT116. Then, we explored the interaction mechanism between CD133+/CD44+ HCT116 and MSCs by the bioinformatics and in vitro assays. After CD133+/CD44+ HCT116 were co-cultured with MSCs, many cytokines in MSCs were stimulated, including interleukin-8 (IL-8). The binding of IL-8/CXCR2 activates the downstream mitogen-activated protein kinase (MAPK) signaling pathway in colon CSCs, thereby promoting the stemness and EMT. However, inhibition of IL-8/CXCR2/Erk1/2 could reverse the effect of MSCs on CSC stemness. In addition, MSCs co-cultured with CD133+/CD44+ HCT116 produce a carcinoma-associated fibroblast phenotype via intracellular FGF10–PKA–Akt–β-catenin signaling, which can be attenuated by IL-8 peptide inhibitor. To conclude, IL-8 promotes the interaction between colon CSCs and MSCs, and activates the MAPK signaling pathway in colon CSCs, which provides a theoretical basis for the application of MSCs in clinical practice. Impact statement MSCs have the property of chemotaxis and they can migrate to the tumor site by paracrine pathway in the tumor environment, and then interact with tumor cells. Although a mass of studies have been conducted about the impact of MSCs on tumors, it is still controversial whether the exogenous MSCs promote or inhibit tumor growth. In this work, we evaluated the effects of MSCs from three sources (bone marrow, adipose, placenta) on the proliferation, stemness, and metastasis of the colon cancer cells both in vitro and in vivo. Then, we proved the IL-8/CXCR2/MAPK and FGF10–PKA–Akt–β-catenin signaling pathway which mediate the interplay between MSC and CD133+/CD44+ colon cancer cell. This research aims to provide a theoretical basis for the safe application of MSCs in the clinical treatment of colon cancer.

scholarly journals Effect of mesenchymal stem cells on cytochrome-c release and inflammation in colon cancer induced by 1,2-dimethylhydrazine in Wistar albino rats

2021 ◽  
Vol 41 (3) ◽  
Author(s):  
Afrah F. Alkhuriji ◽  
Seham G. Alsaiari ◽  
Suliman Y. Alomar ◽  
Alaa A. Alnafjan ◽  
Hussah Alobaid ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Colon Cancer ◽  
Mesenchymal Stem Cells ◽  
Inflammatory Cells ◽  
Redox Status ◽  
Bone Marrow Stem Cells ◽  
Albino Rats ◽  
Cytochrome C Release ◽  
Antitumor Effects

Abstract Colon cancer is one of the most common causes of deaths by cancer worldwide. Stem cells have immunosuppressive properties that promote tumor targeting and circumvent obstacles currently in gene therapy. Bone marrow stem cells are believed to have anticancer potential. The transplantation of mesenchymal stem cells (MSCs), a type of bone marrow stem cells, has been considered a potential therapy for patients with solid tumors due to their capability to enhance the immune response; MSC transplantation has received renewed interest in recent years. The present study aimed to evaluate the antiapoptotic effects of the MSCs on 1,2-dimethylhydrazine (DMH)-induced inflammation in the rat model of colorectal cancer. The rats were randomly allocated into four groups: control, treated with MSCs, induced by DMH, and induced by DMH and treated with MSCs. The MSCs were intra-rectally injected, and DMH was subcutaneously injected at 20 mg/kg body weight once a week for 15 weeks. The administration of MSCs into rats starting from day 0 of the DMH injection was found to enhance the histopathological picture. The MSC treatment resulted in fewer inflammatory cells than in the DMH group. Therefore, our findings suggest that BMCs have antitumor effects by modulating the cellular redox status and down-regulating the pro-inflammatory genes. Thus, BMCs may provide therapeutic value for colon cancer treatment.

scholarly journals In vivo effect of bone marrow-derived mesenchymal stem cells in a rat kidney transplantation model with prolonged cold ischemia

2011 ◽  
Vol 24 (11) ◽  
pp. 1112-1123 ◽  
Author(s):  
Yoshiaki Hara ◽  
Meaghan Stolk ◽  
Jochen Ringe ◽  
Tilo Dehne ◽  
Juliane Ladhoff ◽  
...  
Keyword(s):  
Stem Cells ◽  
Bone Marrow ◽  
Mesenchymal Stem Cells ◽  
Kidney Transplantation ◽  
Rat Kidney ◽  
Cold Ischemia ◽  
Transplantation Model
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