• N. Lukianova R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
  • T. Zadvornyi R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
  • E. Kashuba R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
  • T. Borikun R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
  • О. Mushii R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
  • V. Chekhun R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology



breast cancer, malignancy phenotype, microRNA., osteonectin, osteopontin, prostate cancer


The aim of the study was to compare the expression of markers of bone remodeling in vitro in breast cancer (BCa) cells and prostate cancer (PCa) cells varying in their malignancy phenotype. Materials and Methods: The study was performed on human BCa cells (MCF-7 and MDA-MB-231 lines) and PCa cells (LNCaP and DU-145 lines). Expression levels of bone tissue remodeling proteins (osteopontin (OPN), osteonectin (ON) and bone morphogenetic protein 7 (BMP-7) were determined immunocytochemically. The mRNA levels of bone tissue remodeling proteins OPN (SPP1), ON (SPARC), BMP-7 (BMP7)) and miRNA-10b, -27a, -29b, -145, -146a were assessed by quantitative reverse transcription polymerase chain reaction. To search for miRNAs involved in the regulation of target genes, miRNet v. 2.0 resource was used. Results: We have shown that highly malignant MDA-MB-231 cells are characterized by significantly higher expression of OPN and ON on the background of decreased SPARC and BMP7 mRNA expression. In highly malignant DU-145 cells, ON and SPP1, SPARC, and BMP7 mRNA expression was significantly higher compared with low malignant LNCaP cells. MDA-MB-231 line was characterized by significantly higher expression of miRNA-10b, -27a, -29b, -145 and -146a. In DU-145 cells, significantly lower levels of expression of miRNAs-27a and -145 against the background of increasing levels of miRNAs-29b and -146a were recorded. Conclusion: High malignancy phenotype of the BCa and PCa cells is characterized by high levels of expression of bone remodeling proteins, which may be caused by impaired regulation of their expression at the epigenetic level.


Sung H, Ferlay J, Siegel RL, et al. Global cancer statistics 2020: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2021; 71: 209–49.

Barsouk A, Padala SA, Vakiti A, et al. Epidemiology, staging and management of prostate cancer. Med Sci 2020; 8: 28.

Azamjah N, Soltan-Zadeh Y, Zayeri F. Global trend of breast cancer mortality rate: a 25-year study. APJCP 2019; 20: 2015–20.

Yuan X, Qian N, Ling S, et al. Breast cancer exosomes contribute to pre-metastatic niche formation and promote bone metastasis of tumor cells. Theranostics 2021; 11: 1429–45.

Lin SC, Yu-Lee LY, Lin SH. Osteoblastic factors in prostate cancer bone metastasis. Curr Osteoporos Rep 2018; 16: 642–7.

Berish RB, Ali AN, Telmer PG, et al. Translational models of prostate cancer bone metastasis. Nat Rev Urology 2018; 15: 403–21.

Iglesias-Gato D, Thysell E, Tyanova S, et al. The proteome of prostate cancer bone metastasis reveals heterogeneity with prognostic implications. Clin Cancer Res 2018; 24: 5433–44.

Monteran L, Ershaid N, Sabah I, et al. Bone metastasis is associated with acquisition of mesenchymal phenotype and immune suppression in a model of spontaneous breast cancer metastasis. Sci Rep 2020; 10: 13838.

Sisay M, Mengistu G, Edessa D. The RANK/RANKL/OPG system in tumorigenesis and metastasis of cancer stem cell: potential targets for anticancer therapy. OncoTargets Ther 2017; 10: 3801–10.

Wu X, Li F, Dang L, et al. RANKL/RANK system-based mechanism for breast cancer bone metastasis and related therapeutic strategies. Front Cell Dev Biol 2020; 8: 76.

Christoph F, König F, Lebentrau S, et al. RANKL/RANK/OPG cytokine receptor system: mRNA expression pattern in BPH, primary and metastatic prostate cancer disease. World J Urol 2018; 36: 187–92.

Wong SK, Mohamad N-V, Giaze TR, et al. Prostate cancer and bone metastases: the underlying mechanisms. Int J Mol Sci 2019; 20: 2587.

Pang X, Gong K, Zhang X, et al. Osteopontin as a multifaceted driver of bone metastasis and drug resistance. Pharmacol Res 2019; 144: 235–44.

Si J, Wang C, Zhang D, et al. Osteopontin in bone metabolism and bone diseases. Med Sci Monit 2020; 26: e919159.

Mughal WA, Khalid S, Naseem N, Nagi AH. SPARC in breast carcinomas: a critical review. Biomedica 2020; 36: 109–17.

Zabkiewicz C, Resaul J, Hargest R, et al. Bone morphogenetic proteins, breast cancer, and bone metastases: striking the right balance. Endocr Relat Cancer 2017; 24: R349-R366.

Secondini C, Wetterwald A, Schwaninger R, et al. The role of the BMP signaling antagonist noggin in the development of prostate cancer osteolytic bone metastasis. PloS one 2011; 6: e16078.

Morrissey C, Brown LG, Pitts TE, et al. Bone morphogenetic protein 7 is expressed in prostate cancer metastases and its effects on prostate tumor cells depend on cell phenotype and the tumor microenvironment. Neoplasia 2010; 12: 192–205.

Masuda H, Fukabori Y, Nakano K, et al. Increased expression of bone morphogenetic protein-7 in bone metastatic prostate cancer. The Prostate 2003; 54: 268–74.

Thomas R, True LD, Bassuk JA, et al. Differential expression of osteonectin/SPARC during human prostate cancer progression. Clin Cancer Res 2000; 6: 1140–9.

Forootan SS, Foster CS, Aachi VR, et al. Prognostic significance of osteopontin expression in human prostate cancer. Int J Cancer 2006; 118: 2255–61.

Wang X, Chao L, Ma G, et al. Increased expression of osteopontin in patients with triple‐negative breast cancer. EJCI 2008; 38: 438–46.

Zhu A, Yuan P, Du F, et al. SPARC overexpression in primary tumors correlates with disease recurrence and overall survival in patients with triple negative breast cancer. Oncotarget 2016; 7: 76628–34.

Wang C, Gao C, Zhuang JL, et al. A combined approach identifies three mRNAs that are down-regulated by microRNA-29b and promote invasion ability in the breast cancer cell line MCF-7. J Cancer Res Clin Oncol 2012; 138: 2127–36.

Yan B, Guo Q, Fu FJ, et al. The role of miR-29b in cancer: regulation, function, and signaling. Onco Targets Ther 2015; 8: 539–48.

Kumar S, Keerthana R, Pazhanimuthu A, Perumal P. Overexpression of circulating miRNA-21 and miRNA-146a in plasma samples of breast cancer patients. IJBB 2019; 50: 210–4.

Chekhun VF, Lukianova NY, Chekhun SV, et al. Association of CD44 CD24 /low with markers of aggressiveness and plasticity of cell lines and tumors of patients with breast cancer. Exp Oncol 2017; 39: 203-11.

Zadvornyi TV, Lukianova NY, Borikun TV, Chekhun VF. Effects of exogenous lactoferrin on phenotypic profile and invasiveness of human prostate cancer cells (DU145 and LNCaP) in vitro. Exp Oncol 2018; 40: 184–9.

Chekhun VF, Lukianova NY, Borikun TV, et al. Artemisinin modulating effect on human breast cancer cell lines with different sensitivity to cytostatics. Exp Oncol 2017; 39: 25–9.

McClelland RA, Wilson D, Leake R, et al. A multicentre study into the reliability of steroid receptor immunocytochemical assay quantification. Eur J Cancer Clin Oncol 1991; 27: 711–5.

Fedchenko N, Reifenrath J. Different approaches for interpretation and reporting of immunohistochemistry analysis results in the bone tissue — a review. Diagn Pathol 2014; 9: 221.

Kramer MF. Stem-loop RT-qPCR for miRNAs. Curr Protoc Mol Biol 2011; 95: 10–5.

Zhang JD, Ruschhaupt M, Biczok R. ddCt method for qRT–PCR data analysis. Available from: packages/devel/bioc/vignettes/ddCt/inst/doc/rtPCR.pdf Accessed November 26, 2021.

Chang L, Zhou G, Soufan O, Xia J. miRNet 2.0: network-based visual analytics for miRNA functional analysis and systems biology. Nucl Acids Res 2020; 48: W244–51.

Huang RH, Quan YJ, Chen JH, et al. Osteopontin promotes cell migration and invasion, and inhibits apoptosis and autophagy in colorectal cancer by activating the p38 MAPK signaling pathway. Cell Physiol Biochem 2017; 41: 1851–64.

Chang SH, Minai-Tehrani A, Shin JY, et al. Beclin1-induced autophagy abrogates radioresistance of lung cancer cells by suppressing osteopontin. J Radiat Res 2012; 53: 422–32.

Tuck AB, Chambers AF. The role of osteopontin in breast cancer: clinical and experimental studies. J Mammary Gland Biol Neoplasia 2001; 6: 419–29.

Thalmann GN, Sikes RA, Devoll RE, et al. Osteopontin: possible role in prostate cancer progression. Clin Cancer Res 1999; 5: 2271–7.

Koblinski JE, Kaplan-Singer BR, VanOsdol SJ, et al. Endogenous osteonectin/SPARC/BM-40 expression inhibits MDA-MB-231 breast cancer cell metastasis. Cancer Res 2005; 65: 7370–7.

Gilles C, Bassuk JA, Pulyaeva H, et al. SPARC/osteonectin induces matrix metalloproteinase 2 activation in human breast cancer cell lines. Cancer Res 1998; 58: 5529–36.

Jacob K, Webber M, Benayahu D, Kleinman HK. Osteonectin promotes prostate cancer cell migration and invasion: a possible mechanism for metastasis to bone. Cancer Res 1999; 59: 4453–7.

Alarmo EL, Pärssinen J, Ketolainen JM, et al. BMP7 influences proliferation, migration, and invasion of breast cancer cells. Cancer Lett 2009; 275: 35–43.

Ying X, Sun Y, He P. Bone morphogenetic protein-7 inhibits EMT-associated genes in breast cancer. Cell Physiol Biochem 2015; 37: 1271–8.

Yang S, Lim M, Pham LK, et al. Bone morphogenetic protein 7 protects prostate cancer cells from stress-induced apoptosis via both Smad and c-Jun NH2-terminal kinase pathways. Cancer Res 2006; 66: 4285–90.

Buijs JT, Rentsch CA, van der Horst G, et al. BMP7, a putative regulator of epithelial homeostasis in the human prostate, is a potent inhibitor of prostate cancer bone metastasis in vivo. Am J Pathol 2007; 171: 1047–57.

Creugny A, Fender A, Pfeffer S. Regulation of primary microRNA processing. FEBS Lett 2018; 592: 1980–96.

Ma L, Teruya-Feldstein J, Weinberg R. Tumour invasion and metastasis initiated by microRNA-10b in breast cancer. Nature 2007; 449: 682–8.

Tang Y, Zhang W, Li M, Yan L. miR-10b represses the proliferation and invasion of prostate cancer by targeting LRH1. Int J Clin Exp Pathol 2016; 9: 1424–31.

Jiang G, Shi W, Fang H, Zhang X. miR-27a promotes human breast cancer cell migration by inducing EMT in a FBXW7-dependent manner. Mol Med Rep 2018; 18: 5417–26.

Wan X, Huang W, Yang S, et al. Androgen-induced miR-27A acted as a tumor suppressor by targeting MAP2K4 and mediated prostate cancer progression. Int J Biochem Cell Biol 2016; 79: 249–60.

Zhang B, Shetti D, Fan C, Wei K. miR-29b-3p promotes progression of MDA-MB-231 triple-negative breast cancer cells through downregulating TRAF3. Biological Res 2019; 52: 1–12.

Sur S, Steele R, Shi X, Ray RB. miRNA-29b inhibits prostate tumor growth and induces apoptosis by increasing bim expression. Cells 2019; 8: 1455.

Tang W, Zhang X, Tan W, et al. miR-145-5p suppresses breast cancer progression by inhibiting SOX2. J Surg Res 2019; 236: 278–87.

Zaman MS, Chen Y, Deng G, et al. The functional significance of microRNA-145 in prostate cancer. Br J Cancer 2010; 103: 256–64.

Chen J, Jiang Q, Jiang XQ, et al. miR-146a promoted breast cancer proliferation and invasion by regulating NM23-H1. J Biochem 2020; 167: 41–8.

Lin SL, Chiang A, Chang D, Ying SY. Loss of mir-146a function in hormone-refractory prostate cancer. RNA 2008; 14: 417–24.




How to Cite

Lukianova, N., Zadvornyi, T., Kashuba, E., Borikun, T., Mushii О., & Chekhun, V. (2023). EXPRESSION OF MARKERS OF BONE TISSUE REMODELING IN BREAST CANCER AND PROSTATE CANCER CELLS IN VITRO. Experimental Oncology, 44(1), 39–46.



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