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Current Stem Cell Research & Therapy

Editor-in-Chief

ISSN (Print): 1574-888X
ISSN (Online): 2212-3946

Research Article

Distinctive Expression of MetastamiRs in Breast Cancer Mesenchymal Stem Cells Isolated from Solid Tumor

Author(s): Zahra Sadat Hashemi, Mehdi Forouzandeh Moghadam*, Saeed Khalili, Seyed Mahmoud Hashemi, Koushan Sineh Sepehr and Esmaeil Sadroddiny

Volume 19, Issue 11, 2024

Published on: 22 January, 2024

Page: [1525 - 1534] Pages: 10

DOI: 10.2174/011574888X272313231124063458

Price: $65

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Abstract

Background: MSCs are a part of the tumor microenvironment, which secrete cytokines and chemokines. They can affect metastasis and the growth of tumors. metastamiRs are newly recognized regulatory elements of the metastasis pathway which are involved in epithelial-to-mesenchymal transition (EMT).

Objective: In the present study, we aimed to assess the expression profile of metastamiRs in the context of MSCs in correlation with their invasion and migration power.

Methods: Tumor-isolated BC-MSCs and normal human mammary epithelial cells (HMECs) along with MCF-7, MDA-MB231, and MCF-10A cells were prepared and confirmed for their identity. The cells were assessed for CD44+CD24¯ percentage, Oct-4, and Survivin expression. GEO, KEGG, and TCGA databases were investigated to detect differential miR-expressions. Real- time PCR for 13 miRs was performed using LNA primers. Ultimately, Transwell-Matrigel assays as used to assess the level of migration and invasion.

Results: Our results indicated that some oncomiRs like miR-10b were upregulated in BC-MSCs, while the levels of miR-373 and miR-520c were similar to the MCF-10A. Generally, miR-200 family members were on lower levels compared to the other miR-suppressor (miR-146a, 146b, and 335). miR-31 and 193b were up-regulated in MCF-10A. The most invasiveness was observed in the MDA-MB231 cell line.

Conclusion: We have demonstrated that the miR-expression levels of BC-MSCs are somewhat in between MCF-7 and MDA-MB231 miR-expression levels. This could be the logic behind the moderate level of invasion in BC-MSCs. Therefore, miR-therapy approaches such as miR-mimic or antagomiRs could be used for BC-MSCs in clinical cancer therapy.

Keywords: Breast cancer, metastamiRs, mesenchymal stem cells, cancer stem cell, oncomiRs, lung cancer.

[1]
Sung, H.; Ferlay, J.; Siegel, R.L.; Laversanne, M.; Soerjomataram, I.; Jemal, A.; Bray, F. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J. Clin., 2021, 71(3), 209-249.
[http://dx.doi.org/10.3322/caac.21660] [PMID: 33538338]
[2]
Siegel, R.L.; Miller, K.D.; Jemal, A. Cancer statistics, 2016. CA Cancer J. Clin., 2016, 66(1), 7-30.
[http://dx.doi.org/10.3322/caac.21332] [PMID: 26742998]
[3]
Farokhimanesh, S.; Forouzandeh Moghadam, M.; Ebrahimi, M.; Hashemi, Z.S. Metastasis inhibition by cell type specific expression of BRMS1 gene under the regulation of miR200 family response elements. Cell J., 2021, 23(2), 225-237.
[PMID: 34096224]
[4]
Eccles, S.A.; Welch, D.R. Metastasis: recent discoveries and novel treatment strategies. Lancet, 2007, 369(9574), 1742-1757.
[http://dx.doi.org/10.1016/S0140-6736(07)60781-8] [PMID: 17512859]
[5]
Hatami, Z.; Hashemi, Z.S.; Eftekhary, M.; Amiri, A.; Karpisheh, V.; Nasrollahi, K.; Jafari, R. Natural killer cell-derived exosomes for cancer immunotherapy: innovative therapeutics art. Cancer Cell Int., 2023, 23(1), 157.
[http://dx.doi.org/10.1186/s12935-023-02996-6] [PMID: 37543612]
[6]
Hashemi, Z.S.; Ghavami, M.; Kiaie, S.H.; Mohammadi, F.; Barough, M.S.; Khalili, S.; Hosseini-Farjam, Z.; Mossahebi-Mohammadi, M.; Sheidary, A.; Ghavamzadeh, A.; Forooshani, R.S. Novel delivery of sorafenib by natural killer cell-derived exosomes-enhanced apoptosis in triple-negative breast cancer. Nanomedicine (Lond.), 2023, 18(5), 437-453.
[http://dx.doi.org/10.2217/nnm-2022-0237] [PMID: 37199259]
[7]
Hashemi, Z.S.; Ghavami, M.; Khalili, S.; Naghib, S.M. The Emerging Role of Exosome Nanoparticles in Regenerative Medicine. Nanopharmaceuticals in Regenerative Medicine; CRC Press, 2022, pp. 67-93.
[http://dx.doi.org/10.1201/9781003153504-5]
[8]
Mohammadpour, H.; Khalili, S.; Hashemi, Z.S. Kremen is beyond a subsidiary co-receptor of Wnt signaling: An in silico validation. Turk. J. Biol., 2015, 39(3), 501-510.
[http://dx.doi.org/10.3906/biy-1409-1]
[9]
Hashemi, Z.S.; Moghadam, M.F.; Soleimani, M. Comparison of TGFbR2 down-regulation in expanded HSCs on MBA/DBM scaffolds coated by UCB stromal cells. In Vitro Cell Dev Biol Anim 2015, 51(5), 495-506.
[http://dx.doi.org/10.1007/s11626-014-9854-y] [PMID: 25539863]
[10]
Hashemi, Z.S.; Forouzandeh Moghadam, M.; Soleimani, M.; Hafizi, M.; Amirizadeh, N. TGF-b downregulation by RNAi technique in ex vivo-expanded HSCs on 3D DBM scaffold. Tehran Uni. Med. J., 2012, 70(2)
[11]
Hashemi, Z.S.; Moghadam, M.F.; Farokhimanesh, S.; Rajabibazl, M.; Sadroddiny, E. Inhibition of breast cancer metastasis by co-transfection of miR-31/193b-mimics. Iran. J. Basic Med. Sci., 2018, 21(4), 427-433.
[PMID: 29796229]
[12]
Hashemi, Z.S.; Moghadam, M.F.; Khalili, S.; Ghavami, M.; Salimi, F.; Sadroddiny, E. Additive effect of metastamiR-193b and breast cancer metastasis suppressor 1 as an anti-metastatic strategy. Breast Cancer, 201p, 26(2), 215-228.
[PMID: 30284194]
[13]
Hashemi, Z.S.; Forouzandeh Moghadam, M.; Sadroddiny, E. Varying miR-193b-3p expression patterns in breast cancer cell lines indicates its potential for cancer management strategies. Int. J. Cancer Manag., 2018, 11(8), e63540.
[http://dx.doi.org/10.5812/ijcm.63540]
[14]
Rezaei, T.; Amini, M.; Hashemi, Z.S.; Mansoori, B.; Rezaei, S.; Karami, H. microRNA-181 serves as a dual-role regulator in the development of human cancers. Free Radic. Biol. Med., 2020, 152, 432-454 .
[PMID: 31899343]
[15]
Garofalo, M.; Croce, C.M. microRNAs: Master regulators as potential therapeutics in cancer. Annu. Rev. Pharmacol. Toxicol., 2011, 51(1), 25-43.
[http://dx.doi.org/10.1146/annurev-pharmtox-010510-100517] [PMID: 20809797]
[16]
Langroudi, L.; Forouzandeh, M.; Soleimani, M.; Atashi, A.; Golestaneh, A.F. Induction of differentiation by down-regulation of Nanog and Rex-1 in cord blood derived unrestricted somatic stem cells. Mol. Biol. Rep., 2013, 40(7), 4429-4437.
[http://dx.doi.org/10.1007/s11033-013-2533-3] [PMID: 23661017]
[17]
Goh, J.N.; Loo, S.Y.; Datta, A.; Siveen, K.S.; Yap, W.N.; Cai, W.; Shin, E.M.; Wang, C.; Kim, J.E.; Chan, M.; Dharmarajan, A.M.; Lee, A.S.G.; Lobie, P.E.; Yap, C.T.; Kumar, A.P. MICRORNAS in breast cancer: regulatory roles governing the hallmarks of cancer. Biol. Rev. Camb. Philos. Soc., 2016, 91(2), 409-428.
[http://dx.doi.org/10.1111/brv.12176] [PMID: 25631495]
[18]
Ma, L.; Weinberg, R.A. Micromanagers of malignancy: role of microRNAs in regulating metastasis. Trends Genet., 2008, 24(9), 448-456.
[http://dx.doi.org/10.1016/j.tig.2008.06.004] [PMID: 18674843]
[19]
Nicoloso, M.S.; Spizzo, R.; Shimizu, M.; Rossi, S.; Calin, G.A. MicroRNAs — the micro steering wheel of tumour metastases. Nat. Rev. Cancer, 2009, 9(4), 293-302.
[http://dx.doi.org/10.1038/nrc2619] [PMID: 19262572]
[20]
Choghaei, E.; Khamisipour, G.; Falahati, M.; Naeimi, B.; Mossahebi-Mohammadi, M.; Tahmasebi, R.; Hasanpour, M.; Shamsian, S.; Hashemi, Z.S. Knockdown of microRNA-29a changes the expression of heat shock proteins in breast carcinoma MCF-7 cells. Oncol. Res., 2016, 23(1), 69-78.
[http://dx.doi.org/10.3727/096504015X14478843952906] [PMID: 26802653]
[21]
Calin, G.A.; Croce, C.M. MicroRNA signatures in human cancers. Nat. Rev. Cancer, 2006, 6(11), 857-866.
[http://dx.doi.org/10.1038/nrc1997] [PMID: 17060945]
[22]
Zhang, H.; Li, Y.; Lai, M. The microRNA network and tumor metastasis. Oncogene, 2010, 29(7), 937-948.
[http://dx.doi.org/10.1038/onc.2009.406] [PMID: 19935707]
[23]
Kai, K.; Arima, Y.; Kamiya, T.; Saya, H. Breast cancer stem cells. Breast Cancer, 2010, 17(2), 80-85.
[http://dx.doi.org/10.1007/s12282-009-0176-y] [PMID: 19806428]
[24]
Thompson, E.W.; Haviv, I. The social aspects of EMT-MET plasticity. Nat. Med., 2011, 17(9), 1048-1049.
[http://dx.doi.org/10.1038/nm.2437] [PMID: 21900919]
[25]
Yazdani, S.O.; Pedram, M.; Hafizi, M.; Kabiri, M.; Soleimani, M.; Dehghan, M.M.; Jahanzad, I.; Gheisari, Y.; Hashemi, S.M. A comparison between neurally induced bone marrow derived mesenchymal stem cells and olfactory ensheathing glial cells to repair spinal cord injuries in rat. Tissue Cell, 2012, 44(4), 205-213.
[http://dx.doi.org/10.1016/j.tice.2012.03.003] [PMID: 22551686]
[26]
Sadat Hashemi, Z.; Forouzandeh Moghadam, M.; Soleimani, M. Comparison of the ex vivo expansion of UCB-derived CD34+ in 3D DBM/MBA scaffolds with USSC as a feeder layer. Iran. J. Basic Med. Sci., 2013, 16(10), 1075-1087.
[PMID: 24379965]
[27]
Berthon, P.; Pancino, G.; Cremoux, P.; Roseto, A.; Gespach, C.; Calvo, F. Characterization of normal breast epithelial cells in primary cultures: Differentiation and growth factor receptors studies. In vitro Cell Dev Biol 1992, 28(11-12), 716-724.
[http://dx.doi.org/10.1007/BF02631059] [PMID: 1282913]
[28]
Prat, A.; Perou, C.M. Deconstructing the molecular portraits of breast cancer. Mol. Oncol., 2011, 5(1), 5-23.
[http://dx.doi.org/10.1016/j.molonc.2010.11.003] [PMID: 21147047]
[29]
Prat, A.; Parker, J.S.; Karginova, O.; Fan, C.; Livasy, C.; Herschkowitz, J.I.; He, X.; Perou, C.M. Phenotypic and molecular characterization of the claudin-low intrinsic subtype of breast cancer. Breast Cancer Res., 2010, 12(5), R68.
[http://dx.doi.org/10.1186/bcr2635] [PMID: 20813035]
[30]
Ponti, D.; Costa, A.; Zaffaroni, N.; Pratesi, G.; Petrangolini, G.; Coradini, D.; Pilotti, S.; Pierotti, M.A.; Daidone, M.G. Isolation and in vitro propagation of tumorigenic breast cancer cells with stem/progenitor cell properties. Cancer Res., 2005, 65(13), 5506-5511.
[http://dx.doi.org/10.1158/0008-5472.CAN-05-0626] [PMID: 15994920]
[31]
Hashemi, Z.S.; Khalili, S.; Forouzandeh Moghadam, M.; Sadroddiny, E. Lung cancer and miRNAs: a possible remedy for anti-metastatic, therapeutic and diagnostic applications. Expert Rev. Respir. Med., 2017, 11(2), 147-157.
[http://dx.doi.org/10.1080/17476348.2017.1279403] [PMID: 28118799]
[32]
Huang, Q.; Gumireddy, K.; Schrier, M.; le Sage, C.; Nagel, R.; Nair, S.; Egan, D.A.; Li, A.; Huang, G.; Klein-Szanto, A.J.; Gimotty, P.A.; Katsaros, D.; Coukos, G.; Zhang, L.; Puré, E.; Agami, R. The microRNAs miR-373 and miR-520c promote tumour invasion and metastasis. Nat. Cell Biol., 2008, 10(2), 202-210.
[http://dx.doi.org/10.1038/ncb1681] [PMID: 18193036]
[33]
Heyn, H.; Engelmann, M.; Schreek, S.; Ahrens, P.; Lehmann, U.; Kreipe, H.; Schlegelberger, B.; Beger, C. MicroRNA miR-335 is crucial for the BRCA1 regulatory cascade in breast cancer development. Int. J. Cancer, 2011, 129(12), 2797-2806.
[http://dx.doi.org/10.1002/ijc.25962] [PMID: 21618216]
[34]
Hamel, K.M.; King, C.T.; Cavalier, M.B.; Liimatta, K.Q.; Rozanski, G.L.; King, T.A., Jr; Lam, M.; Bingham, G.C.; Byrne, C.E.; Xing, D.; Collins-Burow, B.M.; Burow, M.E.; Belgodere, J.A.; Bratton, M.R.; Bunnell, B.A.; Martin, E.C. Breast cancer-stromal interactions: adipose-derived stromal/stem cell age and cancer subtype mediated remodeling. Stem Cells Dev., 2022, 31(19-20), 604-620.
[http://dx.doi.org/10.1089/scd.2021.0279] [PMID: 35579936]
[35]
Wei, F.; Cao, C.; Xu, X.; Wang, J. Diverse functions of miR-373 in cancer. J. Transl. Med., 2015, 13(1), 162.
[http://dx.doi.org/10.1186/s12967-015-0523-z] [PMID: 25990556]
[36]
Fath, M.K.; Zahedi, F.; Hashemi, Z.S.; Khalili, S. Evaluation of differentiation quality of several differentiation inducers of bone marrow-derived mesenchymal stem cells to nerve cells by assessing expression of beta-tubulin 3 marker: A systematic review. Curr. Stem Cell Res. Ther., 2021, 16(8), 994-1004.
[http://dx.doi.org/10.2174/1574888X16666210303150814] [PMID: 33655875]
[37]
Jokar, F.; Mahabadi, J.A.; Salimian, M.; Taherian, A.; Hayat, S.M.G.; Sahebkar, A.; Atlasi, M.A. Differential expression of HSP90β in MDA-MB-231 and MCF-7 cell lines after treatment with doxorubicin. J. Pharmacopuncture, 2019, 22(1), 28-34.
[http://dx.doi.org/10.3831/KPI.2019.22.003] [PMID: 30988998]
[38]
Jo, H.; Shim, K.; Jeoung, D. Potential of the miR-200 family as a target for developing anti-cancer therapeutics. Int. J. Mol. Sci., 2022, 23(11), 5881.
[http://dx.doi.org/10.3390/ijms23115881] [PMID: 35682560]
[39]
Zhang, C.; Zhai, W.; Xie, Y.; Chen, Q.; Zhu, W.; Sun, X. Mesenchymal stem cells derived from breast cancer tissue promote the proliferation and migration of the MCF-7 cell line in vitro. Oncol. Lett., 2013, 6(6), 1577-1582.
[http://dx.doi.org/10.3892/ol.2013.1619] [PMID: 24260049]
[40]
Ma, L.; Teruya-Feldstein, J.; Weinberg, R.A. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature, 2007, 449(7163), 682-688.
[http://dx.doi.org/10.1038/nature06174] [PMID: 17898713]
[41]
Karnoub, A.E.; Dash, A.B.; Vo, A.P.; Sullivan, A.; Brooks, M.W.; Bell, G.W.; Richardson, A.L.; Polyak, K.; Tubo, R.; Weinberg, R.A. Mesenchymal stem cells within tumour stroma promote breast cancer metastasis. Nature, 2007, 449(7162), 557-563.
[http://dx.doi.org/10.1038/nature06188] [PMID: 17914389]
[42]
Liu, S.; Ginestier, C.; Ou, S.J.; Clouthier, S.G.; Patel, S.H.; Monville, F.; Korkaya, H.; Heath, A.; Dutcher, J.; Kleer, C.G.; Jung, Y.; Dontu, G.; Taichman, R.; Wicha, M.S. Breast cancer stem cells are regulated by mesenchymal stem cells through cytokine networks. Cancer Res., 2011, 71(2), 614-624.
[http://dx.doi.org/10.1158/0008-5472.CAN-10-0538] [PMID: 21224357]
[43]
Ono, M.; Kosaka, N.; Tominaga, N.; Yoshioka, Y.; Takeshita, F.; Takahashi, R.; Yoshida, M.; Tsuda, H.; Tamura, K.; Ochiya, T. Exosomes from bone marrow mesenchymal stem cells contain a microRNA that promotes dormancy in metastatic breast cancer cells. Sci. Signal., 2014, 7(332), ra63.
[http://dx.doi.org/10.1126/scisignal.2005231] [PMID: 24985346]
[44]
Xavier, P.L.P.; Cordeiro, Y.G.; Rochetti, A.L.; Sangalli, J.R.; Zuccari, D.A.P.C.; Silveira, J.C.; Bressan, F.F.; Fukumasu, H. ZEB1 and ZEB2 transcription factors are potential therapeutic targets of canine mammary cancer cells. Vet. Comp. Oncol., 2018, 16(4), 596-605.
[http://dx.doi.org/10.1111/vco.12427] [PMID: 30047225]
[45]
Song, Y.; Washington, M.K.; Crawford, H.C. Loss of FOXA1/2 is essential for the epithelial-to-mesenchymal transition in pancreatic cancer. Cancer Res., 2010, 70(5), 2115-2125.
[http://dx.doi.org/10.1158/0008-5472.CAN-09-2979] [PMID: 20160041]
[46]
Morrison, G.; Scognamiglio, R.; Trumpp, A.; Smith, A. Convergence of cMyc and β-catenin on Tcf7l1 enables endoderm specification. EMBO J., 2016, 35(3), 356-368.
[http://dx.doi.org/10.15252/embj.201592116] [PMID: 26675138]
[47]
Körner, C.; Keklikoglou, I.; Bender, C.; Wörner, A.; Münstermann, E.; Wiemann, S. MicroRNA-31 sensitizes human breast cells to apoptosis by direct targeting of protein kinase C ϵ (PKCepsilon). J. Biol. Chem., 2013, 288(12), 8750-8761.
[http://dx.doi.org/10.1074/jbc.M112.414128] [PMID: 23364795]
[48]
Fu, Z.; Wang, L.; Li, S.; Chen, F.; Au-Yeung, K.K.W.; Shi, C. MicroRNA as an important target for anticancer drug development. Front. Pharmacol., 2021, 12, 736323.
[http://dx.doi.org/10.3389/fphar.2021.736323] [PMID: 34512363]
[49]
McDermott, A.M.; Heneghan, H.M.; Miller, N.; Kerin, M.J. The therapeutic potential of microRNAs: Disease modulators and drug targets. Pharm. Res., 2011, 28(12), 3016-3029.
[http://dx.doi.org/10.1007/s11095-011-0550-2] [PMID: 21818713]

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