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Clinical and Translational Oncology
Published in: Clinical and Translational Oncology 4/2020

01-04-2020 | Colorectal Cancer | Research Article

Human colorectal cancer derived-MSCs promote tumor cells escape from senescence via P53/P21 pathway

Authors: G. Li, R. Zhang, X. Zhang, S. Shao, F. Hu, Y. Feng

Published in: Clinical and Translational Oncology | Issue 4/2020

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Abstract

Purpose

The purpose of this study was to evaluate effect of MSCs on CRC cell.

Methods

in this study the MSC was isolated from CRC tissue, its effect on CRC cells was investigated in vivo and vitro, and the underlying mechanism was investigated.

Results

In this study we found that MSC-CM could promote colorectal cancer cells escape from senescence both in vitro and in vivo. Further research we demonstrated that MSC-CM acted in colorectal cancer cells senescence through P53/P21 pathway. Next we found that MSC-CM regulate P53 via posttranscription method.

Conclusion

Collectively, these results reveal that MSCs can help colorectal cancer cells defend against senescence through P53/P21 pathway, which may be a new strategy for colorectal cancer therapy.
Literature
1.
Villalobos C, Sobradillo D, Hernandez-Morales M, Nunez L. Calcium remodeling in colorectal cancer. Biochim Biophys Acta. 2017;1864(6):843–9.CrossRef
2.
Shi Y, Du L, Lin L, Wang Y. Tumour-associated mesenchymal stem/stromal cells: emerging therapeutic targets. Nat Rev Drug Discov. 2017;16(1):35–52.CrossRef
3.
Melzer C, Yang Y, Hass R. Interaction of MSC with tumor cells. Cell Commun Signal. 2016;14(1):20.CrossRef
4.
Ferraro GA, De Francesco F, Nicoletti G, Paino F, Desiderio V, Tirino V, D’Andrea F. Human adipose CD34 + CD90 + stem cells and collagen scaffold constructs grafted in vivo fabricate loose connective and adipose tissues. J Cell Biochem. 2013;114(5):1039–49.CrossRef
5.
Dvorak HF. Tumors: wounds that do not heal similarities between tumor stroma generation and wound healing. N Engl J Med. 1986;315(26):1650–9.CrossRef
6.
Dong L, Pu Y, Zhang L, Qi Q, Xu L, Li W, Wei C, Wang X, Zhou S, Zhu J, et al. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles promote lung adenocarcinoma growth by transferring miR-410. Cell Death Discov. 2018;9(2):218.CrossRef
7.
Li W, Zhou Y, Yang J, Zhang X, Zhang H, Zhang T, Zhao S, Zheng P, Huo J, Wu H. Gastric cancer-derived mesenchymal stem cells prompt gastric cancer progression through secretion of interleukin-8. J Exp Clin Cancer Res. 2015;34:52.CrossRef
8.
Wang J, Wang Y, Wang S, Cai J, Shi J, Sui X, Cao Y, Huang W, Chen X, Cai Z, et al. Bone marrow-derived mesenchymal stem cell-secreted IL-8 promotes the angiogenesis and growth of colorectal cancer. Oncotarget. 2015;6(40):42825–37.PubMedPubMedCentral
9.
Koliaraki V, Pallangyo CK, Greten FR, Kollias G. Mesenchymal cells in colon cancer. Gastroenterology. 2017;152(5):964–79.CrossRef
10.
Ohtani N, Mann DJ, Hara E. Cellular senescence: its role in tumor suppression and aging. Cancer Sci. 2009;100(5):792–7.CrossRef
11.
Toso A, Revandkar A, Di Mitri D, Guccini I, Proietti M, Sarti M, Pinton S, Zhang J, Kalathur M, Civenni G, et al. Enhancing chemotherapy efficacy in Pten-deficient prostate tumors by activating the senescence-associated antitumor immunity. Cell Rep. 2014;9(1):75–89.CrossRef
12.
Ventura A, Kirsch DG, McLaughlin ME, Tuveson DA, Grimm J, Lintault L, Newman J, Reczek EE, Weissleder R, Jacks T. Restoration of p53 function leads to tumour regression in vivo. Nature. 2007;445(7128):661–5.CrossRef
13.
Rakhra K, Bachireddy P, Zabuawala T, Zeiser R, Xu L, Kopelman A, Fan AC, Yang Q, Braunstein L, Crosby E, et al. CD4(+) T cells contribute to the remodeling of the microenvironment required for sustained tumor regression upon oncogene inactivation. Cancer Cell. 2010;18(5):485–98.CrossRef
14.
Le Blanc K, Ringden O. Immunobiology of human mesenchymal stem cells and future use in hematopoietic stem cell transplantation. Biol Blood Marrow Transpl. 2005;11(5):321–34.CrossRef
15.
Harris DT. Cord blood stem cells: a review of potential neurological applications. Stem Cell Rev. 2008;4(4):269–74.CrossRef
16.
Pittenger MF, Mackay AM, Beck SC, Jaiswal RK, Douglas R, Mosca JD, Moorman MA, Simonetti DW, Craig S, Marshak DR. Multilineage potential of adult human mesenchymal stem cells. Science. 1999;284(5411):143–7.CrossRef
17.
Wakitani S, Saito T, Caplan AI. Myogenic cells derived from rat bone marrow mesenchymal stem cells exposed to 5-azacytidine. Muscle Nerve. 1995;18(12):1417–26.CrossRef
18.
Kopen GC, Prockop DJ, Phinney DG. Marrow stromal cells migrate throughout forebrain and cerebellum, and they differentiate into astrocytes after injection into neonatal mouse brains. Proc Natl Acad Sci USA. 1999;96(19):10711–6.CrossRef
19.
Ferraro GA, De Francesco F, Nicoletti G, Paino F, Desiderio V, Tirino V, D’Andrea F. Human adipose CD34 + CD90 + stem cells and collagen scaffold constructs grafted in vivo fabricate loose connective and adipose tissues. J Cell Biochem. 2013;114(5):1039–49.CrossRef
20.
Bayati V, Hashemitabar M, Gazor R, Nejatbakhsh R, Bijannejad D. Expression of surface markers and myogenic potential of rat bone marrow- and adipose-derived stem cells: a comparative study. Anat Cell Biol. 2013;46(2):113–21.CrossRef
21.
Lazennec G, Jorgensen C. Concise review: adult multipotent stromal cells and cancer: risk or benefit? Stem Cells. 2008;26(6):1387–94.CrossRef
22.
Hossain A, Gumin J, Gao F, Figueroa J, Shinojima N, Takezaki T, Priebe W, Villarreal D, Kang SG, Joyce C, et al. Mesenchymal stem cells isolated from human gliomas increase proliferation and maintain stemness of glioma stem cells through the IL-6/gp130/STAT3 pathway. Stem Cells. 2015;33(8):2400–15.CrossRef
23.
Li W, Zhou Y, Yang J, Zhang X, Zhang H, Zhang T, Zhao S, Zheng P, Huo J, Wu H. Gastric cancer-derived mesenchymal stem cells prompt gastric cancer progression through secretion of interleukin-8. J Exp Clin Cancer Res. 2015;34:52.CrossRef
24.
Dong L, Pu Y, Zhang L, Qi Q, Xu L, Li W, Wei C, Wang X, Zhou S, Zhu J, et al. Human umbilical cord mesenchymal stem cell-derived extracellular vesicles promote lung adenocarcinoma growth by transferring miR-410. Cell Death Dis. 2018;9(2):218.CrossRef
25.
Zhang X, Hu F, Li G, Li G, Yang X, Liu L, Zhang R, Zhang B, Feng Y. Human colorectal cancer-derived mesenchymal stem cells promote colorectal cancer progression through IL-6/JAK2/STAT3 signaling. Cell Death Dis. 2018;9(2):25.CrossRef
26.
Zheng Y, Wang G, Chen R, Hua Y, Cai Z. Mesenchymal stem cells in the osteosarcoma microenvironment: their biological properties, influence on tumor growth, and therapeutic implications. Stem Cell Res Ther. 2018;9(1):22.CrossRef
27.
Wang G, Fu Y, Hu F, Lan J, Xu F, Yang X, Luo X, Wang J, Hu J. Loss of BRG1 induces CRC cell senescence by regulating p53/p21 pathway. Cell Death Dis. 2017;8(2):e2607.CrossRef
28.
Anwar T, Khosla S, Ramakrishna G. Increased expression of SIRT2 is a novel marker of cellular senescence and is dependent on wild type p53 status. Cell Cycle. 2016;15(14):1883–97.CrossRef
29.
Stein GH, Drullinger LF, Soulard A, Dulic V. Differential roles for cyclin-dependent kinase inhibitors p21 and p16 in the mechanisms of senescence and differentiation in human fibroblasts. Mol Cell Biol. 1999;19(3):2109–17.CrossRef
30.
Dabrowski FA, Burdzinska A, Kulesza A, Sladowska A, Zolocinska A, Gala K, Paczek L, Wielgos M. Comparison of the paracrine activity of mesenchymal stem cells derived from human umbilical cord, amniotic membrane and adipose tissue. J Obstet Gynaecol Res. 2017;43(11):1758–68.CrossRef
Metadata
Title
Human colorectal cancer derived-MSCs promote tumor cells escape from senescence via P53/P21 pathway
Authors
G. Li
R. Zhang
X. Zhang
S. Shao
F. Hu
Y. Feng
Publication date
01-04-2020
Publisher
Springer International Publishing
Published in
Clinical and Translational Oncology / Issue 4/2020
Print ISSN: 1699-048X
Electronic ISSN: 1699-3055
DOI
https://doi.org/10.1007/s12094-019-02152-5

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