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SRC3 expressed in BMSCs promotes growth and migration of multiple myeloma cells by regulating the expression of Cx43

  • Authors:
    • Jie Jin
    • Tao Wang
    • Yu Wang
    • Shidi Chen
    • Zheng Li
    • Xiang Li
    • Jiazhen Zhang
    • Jin Wang
  • View Affiliations / Copyright

    Affiliations: Department of Hematology, The Third Affiliated Daping Hospital of Army Medical University, Chongqing 400042, P.R. China, Institute of Combined Injury, State Key Laboratory of Trauma, Burns and Combined Injury, College of Preventive Medicine, Army Medical University, Chongqing 400038, P.R. China
    Copyright: © Jin et al. This is an open access article distributed under the terms of Creative Commons Attribution License.
  • Pages: 1694-1704
    |
    Published online on: October 20, 2017
       https://doi.org/10.3892/ijo.2017.4171
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Abstract

Interactions between bone marrow stromal cells (BMSCs) and multiple myeloma cells significantly contribute to the progression of multiple myeloma (MM). However, little is known about the molecular mechanisms that regulate these interactions. Connexin-43 (Cx-43) has been implicated in the interplay between BMSCs and MM cells. In this study, we hypothesized that the steroid receptor co-activator-3 (SRC3) expressed in BMSCs regulates the expression of Cx-43 to promote the proliferation and migration of myeloma cells. To address this, we co-cultured a human multiple myeloma cell line, RPMI-8226 transfected with either control BMSCs or sh-SRC3-BMSCs. We found that knocking down SRC3 expression in BMSCs inhibited the proliferation and migration of RPMI-8226 cells. In addition, we found that co-culturing RPMI 8266 cells with BMSCs increased Cx43 expression, while knocking down SRC3 expression in BMSCs decreased Cx43 expression. Moreover, our work revealed that SRC3 in BMSCs regulates Cx43 expression via the mitogen-activated protein kinase (MAPK) pathway. To validate this result in vivo, we knocked down SRC3 expression in BMSCs in nude mice and found that tumor growth and cell apoptosis were significantly decreased. In addition, mice treated with either RPMI 8266 cells overexpressing Cx43 or with a P38 MAPK inhibitor (SB202190) exhibited increased intratumoral leukocyte populations and promoted cell apoptosis in tumor tissue. Our findings demonstrate how SRC3 and Cx43 regulation between BMSCs and myeloma cells mediate cell growth and disease progression, with potential implications for prognosis and therapeutic interventions.
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1 

Falank C, Fairfield H and Reagan MR: Signaling interplay between bone marrow adipose tissue and multiple myeloma cells. Front Endocrinol (Lausanne). 7(Suppl): 672016.

2 

Palumbo A and Anderson K: Multiple myeloma. N Engl J Med. 364:1046–1060. 2011. View Article : Google Scholar : PubMed/NCBI

3 

Zweegman S, Palumbo A, Bringhen S and Sonneveld P: Age and aging in blood disorders: Multiple myeloma. Haematologica. 99:1133–1137. 2014. View Article : Google Scholar : PubMed/NCBI

4 

American Cancer Society: Cancer Facts and Figures 2017. American Cancer Society; Atlanta, GA: 2017, https://www.cancer.org/research/cancer-facts-statistics/all-cancer-facts-figures/cancer-facts-figures-2017.html.

5 

Scheideler M, Elabd C, Zaragosi LE, Chiellini C, Hackl H, Sanchez-Cabo F, Yadav S, Duszka K, Friedl G, Papak C, et al: Comparative transcriptomics of human multipotent stem cells during adipogenesis and osteoblastogenesis. BMC Genomics. 9:3402008. View Article : Google Scholar : PubMed/NCBI

6 

Mahindra A, Hideshima T and Anderson KC: Multiple myeloma: Biology of the disease. Blood Rev. 24(Suppl 1): S5–S11. 2010. View Article : Google Scholar : PubMed/NCBI

7 

Podar K, Chauhan D and Anderson KC: Bone marrow microenvironment and the identification of new targets for myeloma therapy. Leukemia. 23:10–24. 2009. View Article : Google Scholar

8 

Hideshima T, Bergsagel PL, Kuehl WM and Anderson KC: Advances in biology of multiple myeloma: Clinical applications. Blood. 104:607–618. 2004. View Article : Google Scholar : PubMed/NCBI

9 

Xu J and Li Q: Review of the in vivo functions of the p160 steroid receptor coactivator family. Mol Endocrinol. 17:1681–1692. 2003. View Article : Google Scholar : PubMed/NCBI

10 

Manier S, Sacco A, Leleu X, Ghobrial IM and Roccaro AM: Bone marrow microenvironment in multiple myeloma progression. J Biomed Biotechnol. 2012:1574962012. View Article : Google Scholar : PubMed/NCBI

11 

York B, Yu C, Sagen JV, Liu Z, Nikolai BC, Wu RC, Finegold M, Xu J and O'Malley BW: Reprogramming the posttranslational code of SRC-3 confers a switch in mammalian systems biology. Proc Natl Acad Sci USA. 107:11122–11127. 2010. View Article : Google Scholar : PubMed/NCBI

12 

Yan J, Tsai SY and Tsai MJ: SRC-3/AIB1: Transcriptional coactivator in oncogenesis. Acta Pharmacol Sin. 27:387–394. 2006. View Article : Google Scholar : PubMed/NCBI

13 

Jin J, Wang Y, Wang J, Xu Y, Chen S, Wang J, Ran X and Su Y: Increased radiosensitivity and radiation-induced apoptosis in SRC-3 knockout mice. J Radiat Res. 55:443–450. 2014. View Article : Google Scholar :

14 

Jin J, Wang Y, Wang J, Xu Y, Chen SL, Wang JP and Su YP: Impaired hematopoiesis and delayed thrombopoietic recovery following sublethal irradiation in SRC-3 knockout mice. Mol Med Rep. 9:1629–1633. 2014. View Article : Google Scholar : PubMed/NCBI

15 

Warn-Cramer BJ, Cottrell GT, Burt JM and Lau AF: Regulation of connexin-43 gap junctional intercellular communication by mitogen-activated protein kinase. J Biol Chem. 273:9188–9196. 1998. View Article : Google Scholar : PubMed/NCBI

16 

Nimlamool W, Andrews RMK and Falk MM: Connexin43 phosphorylation by PKC and MAPK signals VEGF-mediated gap junction internalization. Mol Biol Cell. 26:2755–2768. 2015. View Article : Google Scholar : PubMed/NCBI

17 

Shishido SN, Delahaye A, Beck A and Nguyen TA: The anticancer effect of PQ1 in the MMTV-PyVT mouse model. Int J Cancer. 134:1474–1483. 2014. View Article : Google Scholar :

18 

Kanczuga-Koda L, Sulkowska M, Koda M, Rutkowski R and Sulkowski S: Increased expression of gap junction protein -connexin 32 in lymph node metastases of human ductal breast cancer. Folia Histochem Cytobiol. 45(Suppl 1): S175–S180. 2007.

19 

Kanczuga-Koda L, Sulkowski S, Tomaszewski J, Koda M, Sulkowska M, Przystupa W, Golaszewska J and Baltaziak M: Connexins 26 and 43 correlate with Bak, but not with Bcl-2 protein in breast cancer. Oncol Rep. 14:325–329. 2005.PubMed/NCBI

20 

Zhou Y, Miao J, Wu H, Tang H, Kuang J, Zhou X, Peng Y, Hu D, Shi D, Deng W, et al: PD-1 and PD-L1 expression in 132 recurrent nasopharyngeal carcinoma: The correlation with anemia and outcomes. Oncotarget. 8:51210–51223. 2017.PubMed/NCBI

21 

Morsing M, Klitgaard MC, Jafari A, Villadsen R, Kassem M, Petersen OW and Rønnov-Jessen L: Evidence of two distinct functionally specialized fibroblast lineages in breast stroma. Breast Cancer Res. 18:1082016. View Article : Google Scholar : PubMed/NCBI

22 

Zhang X, Sun Y, Wang Z, Huang Z, Li B and Fu J: Up-regulation of connexin-43 expression in bone marrow mesenchymal stem cells plays a crucial role in adhesion and migration of multiple myeloma cells. Leuk Lymphoma. 56:211–218. 2015. View Article : Google Scholar

23 

Basak GW, Srivastava AS, Malhotra R and Carrier E: Multiple myeloma bone marrow niche. Curr Pharm Biotechnol. 10:345–346. 2009. View Article : Google Scholar : PubMed/NCBI

24 

Shen X, Guo Y, Yu J, Qi J, Shi W, Wu X, Ni H and Ju S: miRNA-202 in bone marrow stromal cells affects the growth and adhesion of multiple myeloma cells by regulating B cell-activating factor. Clin Exp Med. 16:307–316. 2016. View Article : Google Scholar

25 

Khorasanizadeh M, Eskian M, Gelfand EW and Rezaei N: Mitogen-activated protein kinases as therapeutic targets for asthma. Pharmacol Ther. 174:112–126. 2017. View Article : Google Scholar : PubMed/NCBI

26 

Mugami S, Dobkin-Bekman M, Rahamim-Ben Navi L and Naor Z: Differential roles of PKC isoforms (PKCs) in GnRH stimulation of MAPK phosphorylation in gonadotrope derived cells. Mol Cell Endocrinol. Apr 6–2017.Epub ahead of print. PubMed/NCBI

27 

Segalés J, Perdiguero E and Muñoz-Cánoves P: Regulation of muscle stem cell functions: A focus on the p38 MAPK signaling pathway. Front Cell Dev Biol. 4:912016. View Article : Google Scholar : PubMed/NCBI

28 

Ai XL, Chi Q, Qiu Y, Li HY, Li DJ, Wang JX and Wang ZY: Gap junction protein connexin43 deregulation contributes to bladder carcinogenesis via targeting MAPK pathway. Mol Cell Biochem. 428:109–118. 2017. View Article : Google Scholar : PubMed/NCBI

29 

Losa D, Köhler T, Bellec J, Dudez T, Crespin S, Bacchetta M, Boulanger P, Hong SS, Morel S, Nguyen TH, et al: Pseudomonas aeruginosa-induced apoptosis in airway epithelial cells is mediated by gap junctional communication in a JNK-dependent manner. J Immunol. 192:4804–4812. 2014. View Article : Google Scholar : PubMed/NCBI

30 

Shishido SN and Nguyen TA: Induction of apoptosis by PQ1 a gap junction enhancer that upregulates connexin 43 and activates the MAPK signaling pathway in mammary carcinoma cells. Int J Mol Sci. 17:1782016. View Article : Google Scholar

31 

Geiger PC, Wright DC, Han DH and Holloszy JO: Activation of p38 MAP kinase enhances sensitivity of muscle glucose transport to insulin. Am J Physiol Endocrinol Metab. 288:E782–E788. 2005. View Article : Google Scholar

32 

Uchiyama H, Barut BA, Mohrbacher AF, Chauhan D and Anderson KC: Adhesion of human myeloma-derived cell lines to bone marrow stromal cells stimulates interleukin-6 secretion. Blood. 82:3712–3720. 1993.PubMed/NCBI

33 

Hideshima T, Mitsiades C, Tonon G, Richardson PG and Anderson KC: Understanding multiple myeloma pathogenesis in the bone marrow to identify new therapeutic targets. Nat Rev Cancer. 7:585–598. 2007. View Article : Google Scholar : PubMed/NCBI

34 

Kumar S, Witzig TE, Timm M, Haug J, Wellik L, Fonseca R, Greipp PR and Rajkumar SV: Expression of VEGF and its receptors by myeloma cells. Leukemia. 17:2025–2031. 2003. View Article : Google Scholar : PubMed/NCBI

35 

Nefedova Y, Cheng P, Alsina M, Dalton WS and Gabrilovich DI: Involvement of Notch-1 signaling in bone marrow stroma-mediated de novo drug resistance of myeloma and other malignant lymphoid cell lines. Blood. 103:3503–3510. 2004. View Article : Google Scholar

36 

Mori Y, Shimizu N, Dallas M, Niewolna M, Story B, Williams PJ, Mundy GR and Yoneda T: Anti-alpha4 integrin antibody suppresses the development of multiple myeloma and associated osteoclastic osteolysis. Blood. 104:2149–2154. 2004. View Article : Google Scholar : PubMed/NCBI

37 

Fu J: Cx43 expressed on bone marrow stromal cells plays an essential role in multiple myeloma cell survival and drug resistance. Arch Med Sci. 13:236–245. 2017. View Article : Google Scholar : PubMed/NCBI

38 

Koul HK, Pal M and Koul S: Role of p38 MAP kinase signal transduction in solid tumors. Genes Cancer. 4:342–359. 2013. View Article : Google Scholar : PubMed/NCBI

39 

Chen D, Liu Y, Yang H, Chen D, Zhang X, Fermandes JC and Chen Y: Connexin 43 promotes ossification of the posterior longitudinal ligament through activation of the ERK1/2 and p38 MAPK pathways. Cell Tissue Res. 363:765–773. 2016. View Article : Google Scholar

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Copy and paste a formatted citation
Spandidos Publications style
Jin J, Wang T, Wang Y, Chen S, Li Z, Li X, Zhang J and Wang J: SRC3 expressed in BMSCs promotes growth and migration of multiple myeloma cells by regulating the expression of Cx43. Int J Oncol 51: 1694-1704, 2017.
APA
Jin, J., Wang, T., Wang, Y., Chen, S., Li, Z., Li, X. ... Wang, J. (2017). SRC3 expressed in BMSCs promotes growth and migration of multiple myeloma cells by regulating the expression of Cx43. International Journal of Oncology, 51, 1694-1704. https://doi.org/10.3892/ijo.2017.4171
MLA
Jin, J., Wang, T., Wang, Y., Chen, S., Li, Z., Li, X., Zhang, J., Wang, J."SRC3 expressed in BMSCs promotes growth and migration of multiple myeloma cells by regulating the expression of Cx43". International Journal of Oncology 51.6 (2017): 1694-1704.
Chicago
Jin, J., Wang, T., Wang, Y., Chen, S., Li, Z., Li, X., Zhang, J., Wang, J."SRC3 expressed in BMSCs promotes growth and migration of multiple myeloma cells by regulating the expression of Cx43". International Journal of Oncology 51, no. 6 (2017): 1694-1704. https://doi.org/10.3892/ijo.2017.4171
Copy and paste a formatted citation
x
Spandidos Publications style
Jin J, Wang T, Wang Y, Chen S, Li Z, Li X, Zhang J and Wang J: SRC3 expressed in BMSCs promotes growth and migration of multiple myeloma cells by regulating the expression of Cx43. Int J Oncol 51: 1694-1704, 2017.
APA
Jin, J., Wang, T., Wang, Y., Chen, S., Li, Z., Li, X. ... Wang, J. (2017). SRC3 expressed in BMSCs promotes growth and migration of multiple myeloma cells by regulating the expression of Cx43. International Journal of Oncology, 51, 1694-1704. https://doi.org/10.3892/ijo.2017.4171
MLA
Jin, J., Wang, T., Wang, Y., Chen, S., Li, Z., Li, X., Zhang, J., Wang, J."SRC3 expressed in BMSCs promotes growth and migration of multiple myeloma cells by regulating the expression of Cx43". International Journal of Oncology 51.6 (2017): 1694-1704.
Chicago
Jin, J., Wang, T., Wang, Y., Chen, S., Li, Z., Li, X., Zhang, J., Wang, J."SRC3 expressed in BMSCs promotes growth and migration of multiple myeloma cells by regulating the expression of Cx43". International Journal of Oncology 51, no. 6 (2017): 1694-1704. https://doi.org/10.3892/ijo.2017.4171
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