• T. Zadvornyi R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
  • N. Lukianova R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
  • T. Borikun R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
  • S. Gogol R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
  • P. Virych R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
  • O. Lykhova R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology
  • V. Chekhun R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology



breast cancer, doxorubicin, osteonectin, osteopontin, prostate cancer


Background: According to modern literature, osteopontin (OPN) and osteonectin (ON) are involved not only in the formation of the aggressive phenotype of malignantly transformed cells, but also in the realization of cytotoxic effects of some antitumor drugs. Aim: To study the changes of the expression of OPN and ON and their mRNAs (SPP1 and SPARC) upon exposure to doxorubicin (Dox) in breast cancer (BCa) and prostate cancer (PCa) cell lines with different sensitivity to Dox. Materials and Methods: Cell lines of BCa (MCF-7 and MDA-MB-231) and PCa (LNCaP and DU-145) were cultured in the presence of Dox at IC30 concentrations for 24 h. OPN and ON levels were assessed by immunocytochemical (ICH) and Western blot analysis. SPP1 and SPARC mRNA levels were assessed by quantitative PCR. Results: Dox treatment resulted in the significant decrease in the expression of both OPN and ON in MCF-7 and LNCaP cells. Similarly, Dox treatment downregulated both SPP1 and SPARC in MDA-MB-231 and DU-145 cells. Dox did not affect ON expression in MDA-MB-231 and DU-145 cells although the significant decrease in the level of SPARC mRNA has been evident. In contrast, no significant differences in SPP1 and SPARC mRNA levels were detected in LNCaP cells. Conclusion: The changes in the expression of OPN and ON proteins and their corresponding genes in BCa and PCa cells may be related to the intrinsic mechanisms of Dox effects in cells differing by malignant phenotype and Dox sensitivity.


Sopik V. International variation in breast cancer incidence and mortality in young women. Breast Cancer Res Treat 2021; 186: 497–507.

Wilkinson L, Gathani T. Understanding breast cancer as a global health concern. Br J Radiol 2022; 95: 20211033.

Pernar CH, Ebot EM, Wilson KM, et al. The epidemiology of prostate cancer. Cold Spring Harb. perspect. med. 2018; 8: a030361.

Sparano JA, Gray RJ, Ravdin PM, et al. Clinical and genomic risk to guide the use of adjuvant therapy for breast cancer. N Engl J Med 2019; 380: 2395–40.

Tolkach Y, Kristiansen G. The heterogeneity of prostate cancer: a practical approach. Pathobiology 2018; 85: 108–16.

Ramos P, Bentires-Alj M. Mechanism-based cancer therapy: resistance to therapy, therapy for resistance. Oncogene 2015; 34: 3617–26.

Beltran H, Hruszkewycz A, Scher HI, et al. The role of lineage plasticity in prostate cancer therapy resistance. Clin Cancer Res 2019; 25: 6916–24.

Nakazawa M, Paller C, Kyprianou N. Mechanisms of therapeutic resistance in prostate cancer. Curr Oncol Rep 2017; 19: 1–12.

Shoag J, Barbier CE. Clinical variability and molecular heterogeneity in prostate cancer. Asian J Androl 2016; 18: 543–8.

Lüönd F, Tiede S, Christofori G. Breast cancer as an example of tumour heterogeneity and tumour cell plasticity during malignant progression. Br J Cancer 2021; 125: 164–75.

Gerarduzzi C, Hartmann U, Leask A, Drobetsky E. The matrix revolution: matricellular proteins and restructuring of the cancer microenvironment. Cancer Res 2020; 80: 2705–17.

Bradshaw AD. Diverse biological functions of the SPARC family of proteins. Int J Biochem Cell Biol 2012; 44: 480–8.

Lukianova N, Zadvornyi T, Kashuba E, et al. Expression of markers of bone tissue remodeling in breast cancer and prostate cancer cells in vitro. Exp Oncol 2022; 44: 39–46.

Kaleağasıoğlu F, Berger MR. SIBLINGs and SPARC families: their emerging roles in pancreatic cancer. World J Gastroenterol 2014; 20: 14747–59.

Icer MA, Gezmen-Karadag M. The multiple functions and mechanisms of osteopontin. Clin Biochem 2018; 59: 17–24.

Si J, Wang C, Zhang D, et al. Osteopontin in bone metabolism and bone diseases. Med Sci Monit 2020; 26: e919159-1.

Singh A, Gill G, Kaur H, et al. Role of osteopontin in bone remodeling and orthodontic tooth movement: a review. Prog Orthod 2018; 19: 1–8.

Zhu YS, Gu Y, Jiang C, Chen L. Osteonectin regulates the extracellular matrix mineralization of osteoblasts through P38 signaling pathway. J Cell Physiol 2020; 235: 2220–31.

Motamed K. SPARC (osteonectin/BM-40). Int J Biochem Cell Biol 1999; 31: 1363–6.

Bao LH, Sakaguchi H, Fujimoto J, Tamaya T. Osteopontin in metastatic lesions as a prognostic marker in ovarian cancers. J Biomed Sci 2007; 14: 373–81.

Imano M, Satou T, Itoh T, et al. Immunohistochemical expression of osteopontin in gastric cancer. J Gastrointest Surg 2009; 13: 1577–82.

Lin F, Li Y, Cao J, et al. Overexpression of osteopontin in hepatocellular carcinoma and its relationships with metastasis, invasion of tumor cells. Mol Biol Rep 2011; 38: 5205–10.

Zhao B, Sun T, Meng F, et al. Osteopontin as a potential biomarker of proliferation and invasiveness for lung cancer. J Cancer Res Clin Oncol 2011; 137: 1061–70.

Chen Y, Zhang Y, Tan Y, Liu Z. Clinical significance of SPARC in esophageal squamous cell carcinoma. Biochem Biophys Res Commun 2017; 492: 184–91.

Lindner JL, Loibl S, Denkert C, et al. Expression of secreted protein acidic and rich in cysteine (SPARC) in breast cancer and response to neoadjuvant chemotherapy. Ann Oncol 2015; 26: 95–100.

Papapanagiotou A, Sgourakis G, Karkoulias K, et al. Osteonectin as a screening marker for pancreatic cancer: A prospective study. Int J Med Res 2018, 46: 2769–79.

Lewis JS, Thorstad, WL, Hussaini M. Osteonectin/SPARC expression in head and neck squamous cell carcinoma: a tissue microarray study. Appl Immunohistochem Mol Morphol 2022; 30: 317–25.

Komar G, Kauhanen S, Liukko K, et al. Decreased blood flow with increased metabolic activity: a novel sign of pancreatic tumor aggressiveness. Clin Cancer Res 2009; 15: 5511–8.

Schunke KJ, Coyle L, Merrill GF, Denhardt DT. Acetaminophen attenuates doxorubicin‐induced cardiac fibrosis via osteopontin and GATA 4 regulation: Reduction of oxidant levels. J Cell Physiol 2013; 228: 2006–14.

Graessmann M, Berg B, Fuchs B, et al. Chemotherapy resistance of mouse WAP-SVT/t breast cancer cells is mediated by osteopontin, inhibiting apoptosis downstream of caspase-3. Oncogene 2007; 26: 2840–50.

Brum MC, Guimaräes IS, Ferreira LB, et al. Osteopontin-c mediated drug resistance in breast and ovarian carcinoma cells. Cancer Res 2018; 78: 4453.

Dhanesuan N, Sharp JA, Blick T, et al. (2002). Doxycycline-inducible expression of SPARC/Osteonectin/BM40 in MDA-MB-231 human breast cancer cells results in growth inhibition. Breast Cancer Res Treat 2002; 75: 73–85.

Yang MC, Wang HC, Hou YC, et al. Blockade of autophagy reduces pancreatic cancer stem cell activity and potentiates the tumoricidal effect of gemcitabine. Mol Cancer 2015; 14: 179.

Pang H, Cai L, Yang Y, et al. Knockdown of osteopontin chemosensitizes MDA-MB-231 cells to cyclophosphamide by enhancing apoptosis through activating p38 MAPK pathway. Cancer Biother Radiopharm 2011; 26: 165–73.

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.

Lukianova NY, Andriiv AV, Chekhun VF. Correlation of iodine symporter expression in highly and low malignant cell lines of human breast cancer differed in their sensitivity to doxorubicin. Exp Oncol 2016; 38: 169–71.

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.

Laemmli UK. Cleavage of structural proteins during the assembly of the head of bacteriophage T4. Nature 1970; 227: 680–5.

Sovak M, Bellas R, Kim D, et al. Aberrant nuclear factor-kB/Rel expression and pathogenesis of breast cancer. J Clin Invest 1997; 100: 2952–60.

Bradford M. A rapid and sensitive method for the quantification of microgram quantities of protein utilizing the principle of protein-dye binding. Annal Biochem 1976; 72: 248–54.

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

Khan SA, Cook AC, Kappil M, et al. Enhanced cell surface CD44 variant (v6, v9) expression by osteopontin in breast cancer epithelial cells facilitates tumor cell migration: novel post-transcriptional, post-translational regulation. Clin Exp Metastasis 2005; 22: 663–73.

Menezes MC, O’Neil A, Guimaraes I, et al. Expression of osteopontin splicing isoforms in prostate cancer cells resistant to docetaxel. Cancer Res 2016; 76: 2937.

Luo SD, Chen YJ, Liu CT, et al. Osteopontin involves cisplatin resistance and poor prognosis in oral squamous cell carcinoma. BioMed Res Int 2015; 2015: 508587.

Chen X, Xiong D, Ye L, et al. SPP1 inhibition improves the cisplatin chemosensitivity of cervical cancer cell lines. Cancer Chemother Pharmacol 2019; 83: 603–13.

Tajima K, Ohashi R, Sekido Y, et al. Osteopontin-mediated enhanced hyaluronan binding induces multidrug resistance in mesothelioma cells. Oncogene 2010; 29: 1941–51.

Shen CJ, Tsou YA, Chen HL, et al. Osteoponin promoter controlled by DNA methylation: aberrant methylation in cloned porcine genome. BioMed Res Internat 2014; 2014: 1–16.

Chekhun VF, Borikun TV, Lukianova NYu. Effect of 5-azacytidine on miRNA expression in human breast cancer cells with different sensitivity to cytostatics. Exp Oncol 2016; 38: 26–30.




How to Cite

Zadvornyi, T., Lukianova, N., Borikun, T., Gogol, S., Virych, P., Lykhova, O., & Chekhun, V. (2023). EXPRESSION OF OSTEOPONTIN AND OSTEONECTIN IN BREAST AND PROSTATE CANCER CELLS WITH DIFFERENT SENSITIVITY TO DOXORUBICIN. Experimental Oncology, 44(2), 107–112.



Original contributions

Most read articles by the same author(s)

1 2 > >>