EXPERIMENTAL EVALUATION OF INFLUENCE OF IMPLANTATION MATERIALS BASED ON CALCIUM PHOSPHATES ON MOLECULAR-BIOLOGICAL CHARACTERISTICS OF NORMAL AND MALIGNANT TRANSFORMED CELLS OF HORMONE-DEPENDENT TUMORS
DOI:
https://doi.org/10.32471/oncology.2663-7928.t-22-3-2020-g.9225Keywords:
adhesion, bone metastasis, breast cancer, implant materials, miRNA, prostate cancer, receptor statusAbstract
Aim: to study the effect of implant materials (IM) based on calcium phosphates on the molecular biological characteristics of normal and malignantly transformed hormone-dependent cells in the in vitro system. Objects and methods: cells of normal human fibroblasts, prostate cancer lines (LNCaP and DU-145) and breast cancer (MCF-7, MDA-MB-231) were cultured with IM at a dose corresponding to IC30 (100 μg/ml) during 48 hours. Expression levels of molecular markers were determined by immunocytochemical method. MicroRNA levels were assessed by quantitative PCR. Analysis of functional relationships and interactions between experimental molecules was performed using the STRING v.11.0 algorithm. Statistical analysis of the results was performed using the Statistics 6.0. Software. Results: the analysis of cytomorphological features of cells exposed to IM revealed a unidirectional change that indicate an increase in their adhesive properties, as evidenced by the increase in expression of E- and N-cadherin in cells of human breast and prostate cancer cells. It was found that under the action of the tested substance in the cancer cells is an increase in the expression of oncogenic miRNA-221, which reduces the level of steroid hormone receptors. It was determined that IM does not affect the receptor status, the expression of adhesion molecules and Ki-67 in cells of normal fibroblasts. Conclusions: the cultivation of malignantly transformed cells of the human breast cancer and prostate cancer with IM leads to a decrease in their invasive properties due to changes in cytoarchitectonics and adhesive characteristics. The established changes in the posttranscriptional regulation of proteins associated with receptor status in the cells of breast and prostate cancer under the influence of phosphate-based IM require further research.
References
Lyubimova NV, Kushlinsky NЕ. Biochemical markers of bone metastasis. Advances mol oncol 2015; (1): 61–75 (in Russian).
Chen Y-C, Sosnoski DM, Mastro AM. Breast cancer metastasis to the bone: mechanisms of bone loss. Breast cancer res 2010; 12: 215–25.
Gartrell BA, Coleman R, Efstathiou E, et al. Metastatic prostate cancer and the bone: significance and therapeutic options. European Urol 2015; 68 (5): 850–8.
Moiseenko VM, Blinov NN. Metastatic bone disease in solid tumors and the possibility of using clodronate (Bonefos) in clinical oncology (literature review). SPb, 1995. 47 c. (in Russian).
Bondarenko IM, Asєєv OI, Dmitrenko KO. Pre-treatment factors in the prognosis of the effectiveness of hormone therapy for metastatic breast cancer in menopausal ailments. Topical issues of pharmaceutical and medical science and practice 2008; 21 (1): 8–14 (in Ukrainian).
Bray F, Ferlay J, Soerjomataram I, et al. Global cancer statistics 2018: GLOBOCAN estimates of incidence and mortality worldwide for 36 cancers in 185 countries. CA Cancer J Clin 2018; 68 (6): 394–424.
Cancer in Ukraine, 2016–2017. Incidence, mortality, activities of oncological service. Bulletin of national cancer registry of Ukraine, № 19, Кyiv, 2018. 131 p.
Kampova-Polevaya EB, Chistyakova SS. Clinical mammology: current state of the problem. GEOTAR-Media, 2006. 399 p. (in Russian).
Aapro SM. Denosumab for bone metastases from breast cancer: a new therapy option? J clin oncol 2011; l14: 1419–20.
Moiseenko VM. Palliative treatment of patients with solid tumors with metastatic bone lesions. Practical oncology 2001; 1 (5): 33–8.
Ashkar S, Weber GF, Panoutsakopoulou V, et al. Eta-1(osteopontin): an early component of type-1 (cell-mediated) immunity. Science 2000; 287 (5454): 860–4.
Denhardt DT, Noda M, O’Regan AW, et al. Osteopontin as a means to cope with environmental insults: regulation of inflammation, tissue remodeling, and cell survival. J Clin Invest 2001; 107 (9): 1055–61.
Mazzali M, Kipari T, Ophascharoensuk V, et al. Osteopontin — a molecule for all seasons. QJM 2002; 95 (1): 3–13.
Amiraslanov AT, Amiraslanov AA, Ibragimov EE, et al. Types of complications in arthroplasty of large joints in patients with bone tumors. Bulletin of the Russian Oncology Center NN Blokhin RAM 2009; 20 (1): 17–21 (in Russian).
Shevchenko SD. Organ-preserving operations for malignant bone tumors in children. International medical journal 2009; (1): 75–9 (in Russian).
Orimo A, Gupta PB, Sgroi DC, et al. Stromal fibroblasts present in invasive human breast carcinomas promote tumor growth and angiogenesis through elevated SDF-1/CXCL12 secretion. Cell 2005; 121 (3): 335–48.
Condeelis J, Pollard JW. Macrophages: obligate partners for tumor cell migration, invasion, and metastasis. Cell 2006;124 (2): 263–6.
Guerrieri AN, Montesi M, Sprio S, et al. Innovative options for bone metastasis treatment: an extensive analysis on biomaterials-based strategies for orthopedic surgeons. Front Bioeng Biotechnol 2020; 8: 589964.
McClelland RA, Wilson D, Leake R., et al. A multicentre study into the reliability of steroid receptor immunocytochemical assay quantification. European J Cancer Clin Oncol 1991; 27 (6): 711–15.
Fedchenko N, Reifenrath J. Different approaches for interpretation and reporting of immunohistochemistry analysis results in the bone tissue — a review. Diag pathol 2014; 9: 221.
Kramer MF. Stem‐loop RT‐qPCR for miRNAs. Current protocols in molecular biology 2011; 95 (1): 15–20.
Torres A, Torres K., Wdowiak P, et al. Selection and validation of endogenous controls for microRNA expression studies in endometrioid endometrial cancer tissues. Gynecol oncol 2013; 130 (3): 588–94.
Nicoloso MS, Spizzo R, Shimizu M, et al. MicroRNAs–the micro steering wheel of tumour metastases. Nat Rev Cancer 2009; 9 (4): 293–302.
Heneghan HM, Miller N, Kerin MJ. MiRNAs as biomarkers and therapeutic targets in cancer. Curr Opin Pharmacol 2010; 10 (5): 543–550.
Journé F, Dumon JC, Kheddoumi N, et al. Extracellular calcium downregulates estrogen receptor alpha and increases its transcriptional activity through calcium-sensing receptor in breast cancer cells. Bone 2004; 35 (2): 479–88.
Gong YUEWEN, Blok LJ, Perry JE, et al.Calcium regulation of androgen receptor expression in the human prostate cancer cell line LNCaP. Endocrinol 1995; 136 (5): 2172–8.
Morgan MP, Cooke MM, Christopherson PA, et al. Calcium hydroxyapatite promotes mitogenesis and matrix metalloproteinase expression in human breast cancer cell lines. Mol Carcinogenesis 2001; 32 (3): 111–7.
