Morphology and proliferation of bone marrow mesenchymal stem cells and expressions of CD34 and CD44 under stomach cancer microenvironment

doi:10.3969/j.issn.2095-4344.2016.14.009

Abstract

Abstract:

BACKGROUND: Gastric cancer mesenchyal stem cells from clinical stomach cancer specimens and tumorigenic tissues in nude mice are similar to the bone marrow mesenchymal stem cells in biological characteristics, which have been proved to be an important component of tumor microenvironment to promote tumor growth. It is speculated that biological characteristic of bone marrow mesenchymal stem cells may change in stomach cancer microenvironment.

OBJECTIVE: To observe the effect of stomach cancer microenvironment on morphology and proliferation of bone marrow mesenchymal stem cells and expressions of CD34 and CD44.

METHODS: Rat bone marrow mesenchymal stem cells were cultured alone as control group. In the test group, rat bone marrow mesenchymal stem cells were co-cultured with human stomach cancer BGC-823 cells using Transwell chamber assay to establish the stomach cancer microenvironment. Then, cell morphology, proliferation, cell cycle and CD34, CD44 expressions were observed and detected using inverted phase contrast microscope, MTT assay, and flow cytometry, respectively.

RESULTS AND CONCLUSION: In the test group, bone marrow mesenchymal stem cells were similar to human stomach cancer cells BGC-823 that arranged disorderly and irregularly, were interconnected loosely, became thinner and longer, and grew in clusters with smaller nuclei. The cell proportion in G₁ phase significantly decreased, but that in S and G₂/M phases significantly increased (P < 0.01, P < 0.05). The positive rate of CD44 significantly declined, and the CD34 expression significantly raised (P < 0.01). In conclusion, stomach cancer microenvironment by non-contact co-culture with BCG-823 cells has an obvious effect on the morphology, proliferation and surface antigens expressions of bone marrow mesenchymal stem cells that will tend to be malignant gastric cancer cells.
中国组织工程研究杂志出版内容重点：干细胞；骨髓干细胞；造血干细胞；脂肪干细胞；肿瘤干细胞；胚胎干细胞；脐带脐血干细胞；干细胞诱导；干细胞分化；组织工程

Key words: Mesenchymal Stem Cells, Cell Proliferation, CD34, CD44, Tissue Engineering

Wu Gao-feng, Liu Xi-ping, Yang Bai-lin, Li Pei-qing, Ming Hai-xia, Zhang Wei. Morphology and proliferation of bone marrow mesenchymal stem cells and expressions of CD34 and CD44 under stomach cancer microenvironment[J]. Chinese Journal of Tissue Engineering Research, 2016, 20(14): 2040-2045.

Figures/Tables 7

References

[1] Nakamizo A,Marini F,Amano T,et al.Human bone marrow-derived mesenchymal stemcell in the treatment of gliomas.Cancer Res.2005;65(8): 3307-3318.

[2] Nakamura K,Ito Y,Kawano Y,et al.Anti-tumor effect of genetically engineered Mesenchymal stem cells in a rat gliomas.Gene Therapy.2004;11(14):1155-1164.

[3] Studeny M,Marini FC,Dembinski JL,et al.Mesenchymal Stem Cells:potential precursors for tumor stroma and targeted-delivery vehiclesfor anticancer agents.J Natl Cancer Inst.2004;96(21):1593-1603.

[4] Miuraa M,Miura Y,Padilla-Nash HM,et al.Accumulated chromo-somal instability in murine bone marrow mesenchymal stem cells tomalignant transformation. Stemcell.2006;24(4):1095-1103.

[5] Rosland GV,Svendsen A,Torsvik A ,et al.Long-term cultures of bone marrow derived human　mesenchymal stem cells frequently un-dergo spontaneous malignant transformation.Cancer Res.2009;69(13):5331-5339.

[6] Laconi E.The evolving concept of tumor microenvironments.Bioessays.2007;29(8):738-744.

[7] Bexell D, Gunnarsson S, Tormin A, et a1.Bone marrow mu1potent mesenchym al storm a cells act as pericyte-1ike migratory vehicles in experim ental gliomas.Molecular Therapy.2009;17(6):183-190

[8] Bergfeld SA,DeClerck YA.Bone marrow- derived mesenchymal stem cells and the tumor microenvironment. Cancer Metastasis Rev.2010;29( 2): 249 -261.

[9] 张亚兰,朱静,田杰,等.肿瘤微环境中间充质干细胞的相关生物学特性分析.解放军医学杂志,2010,35(1):67-70.

[10] 刘永琦,王倩,秦洁,等.肿瘤微环境对骨髓间充质干细胞形态、生长及增殖的影响[J].中国细胞生物学学报,2013, 35(2):180-187.

[11] 景明,陈正君,王雅莉,等.结肠癌微环境对骨髓间充质干细胞形态、增殖及CD13、CD133表达的影响,2014,33(9): 497-500.

[12] Ogasawara N, Tsukamoto T, Inada K, et al.Frequent c-Kit gene mutations not only in gastrointestinal stromal tumors but also in intersti-tial cells of Cajal in surrounding normal mucosa.Cancer Lett.2005;230(2): 199-210

[13] Houghton J, Stoicov C, Nomura S, et al.Gastric cancer originating from bone marrow-derived cells.Science. 2004; 306(3):1568-1571

[14] 李争艳,刘杨,翟丽丽,等.胃癌细胞 SGC-7901对骨髓来源的间充质干细胞作用的研究[J].临床与实验病理学杂志,2011,27(8):856-859

[15] Jones DL ,Wagers AJ.No place like home:anatomy and function of the stem cell niche.Nature Reviews Molecular Cell Biology.2008;9(1):11-21.

[16] De Ugarte DA, Alfonso Z, Zuk PA, et al.Differential expression of stem cell mobilization-associated molecules on multi-lineage cells from adipose tissue and bone marrow.Immunol Lett.2003;89(3): 267.

[17] Shahdadfar A, Fronsdal K, Haug T, et al.In vitro expansion of human mesenchymal stem cells choice of serum is a determinant of cell proliferation, differentiation, gene expression, and transcriptome stability.Stem Cells.2005;23(9): 1357-1366.