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. 2024 Apr;105(4):252-265.
doi: 10.1002/cyto.a.24814. Epub 2024 Jan 16.

Human mesenchymal stem cells increase LLC metastasis and stimulate or decelerate tumor development depending on injection method and cell amount

Yurii V Stepanov  1   2 , Iuliia Golovynska  1 , Galyna Ostrovska  3 , Larysa Pylyp  4 , Taisa Dovbynchuk  3 , Liudmyla I Stepanova  3 , Oleksandr Gorbach  5 , Volodymyr Shablii  6   7 , Hao Xu  1 , Liudmyla V Garmanchuk  3 , Tymish Y Ohulchanskyy  1 , Junle Qu  1 , Galina I Solyanik  2
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Free article

Human mesenchymal stem cells increase LLC metastasis and stimulate or decelerate tumor development depending on injection method and cell amount

Yurii V Stepanov et al. Cytometry A. 2024 Apr.
Free article

Abstract

Mesenchymal stem cells (MSCs) being injected into the body can stimulate or decelerate carcinogenesis. Here, the direction of influence of human placenta-derived MSCs (P-MSCs) on the Lewis lung carcinoma (LLC) tumor development and metastatic potential is investigated in C57BL/6 mice depending on the injection method. After intramuscular co-inoculation of LLC and P-MSCs (LLC + P-MSCs), the growth of primary tumor and angiogenesis are slowed down compared to the control LLC on the 15th day. This is explained by the fact of a decrease in the secretion of proangiogenic factors during in vitro co-cultivation of an equal amount of LLC and P-MSCs. When P-MSCs are intravenously (i.v.) injected in the mice with developing LLC (LLC + P-MSCs(i.v.)), the tumor growth and angiogenesis are stimulated on the 15th day. A highly activated secretion of proangiogenic factors by P-MSCs in a similar in vitro model can explain this. In both the models compared to the control on the 23rd day, there is no significant difference in the tumor growth, while angiogenesis remains correspondingly decelerated or stimulated. However, in both the models, the total volume and number of lung metastases constantly increase compared to the control: it is mainly due to small-size metastases for LLC + P-MSCs(i.v.) and larger ones for LLC + P-MSCs. The increase in the rate of LLC cell dissemination after the injection of P-MSCs is explained by the disordered polyploidy and chromosomal instability, leading to an increase in migration and invasion of cancer cells. After LLC + P-MSCs co-inoculation, the tumor cell karyotype has the most complex and heterogeneous chromosomal structure. These findings indicate a bidirectional effect of P-MSCs on the growth of LLC in the early periods after injection, depending on the injection method, and, correspondingly, the number of contacting cells. However, regardless of the injection method, P-MSCs are shown to increase LLC aggressiveness related to cancer-associated angiogenesis and metastasis activation in the long term.

Keywords: Lewis lung carcinoma karyotype; angiogenesis; cancer; human mesenchymal stem cells; tumor growth and metastasis.

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References

REFERENCES

    1. Studeny M, Marini FC, Dembinski JL, Zompetta C, Cabreira‐Hansen M, Bekele BN, et al. Mesenchymal stem cells: potential precursors for tumor stroma and targeted‐delivery vehicles for anticancer agents. J Natl Cancer Inst. 2004;96(21):1593–1603.
    1. Klopp AH, Spaeth EL, Dembinski JL, Woodward WA, Munshi A, Meyn RE, et al. Tumor irradiation increases the recruitment of circulating mesenchymal stem cells into the tumor microenvironment. Cancer Res. 2007;67(24):11687–11695.
    1. Sun Z, Wang S, Zhao R. The roles of mesenchymal stem cells in tumor inflammatory microenvironment. J Hematol Oncol. 2014;7(1):14.
    1. Zhu W, Xu W, Jiang R, Qian H, Chen M, Hu J, et al. Mesenchymal stem cells derived from bone marrow favor tumor cell growth in vivo. Exp Mol Pathol. 2006;80(3):267–274.
    1. Karnoub AE, Dash AB, Vo AP, Sullivan A, Brooks MW, Bell GW, et al. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature. 2007;449(7162):557–563.

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