RELATION BETWEEN LACTOFERRIN LEVELS AND MOLECULAR BIOLOGICAL FEATURES OF BREAST MALIGNANT TUMORS

Authors

  • S.O. Sobchenko Kyiv City Clinical Oncology Center
  • N.Yu. Lukianova R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
  • V.M. Bazas Kyiv City Clinical Oncology Center
  • T.V. Zadvorny R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine
  • О.М. Kliusov Kyiv City Clinical Oncology Center
  • V.F. Chekhun R.E. Kavetsky Institute of Experimental Pathology, Oncology and Radiobiology, National Academy of Sciences of Ukraine, Kyiv, Ukraine

DOI:

https://doi.org/10.32471/oncology.2663-7928.t-23-1-2021-g.9456

Keywords:

breast cancer, lactoferrin., molecular biological features

Abstract

Aim: to analyze the dependence of lactoferrin (LF) levels in serum and patient’s tumor cells on the expression of molecular biomarkers in breast cancer (BC) cells and survival rates. Object and methods: clini­cal samples of 151 patients with stage I–II BC were analyzed in the study; clinical, morphological, immunohistochemical, enzyme-linked immunosorbent assay and statistical methods were applied. Results: in BC patients, the heterogeneity of lactoferrin levels at the tumor and body level was demonstrated. It was determined that there is a statistically significant correlation between the lactoferrin level in blood serum and its expression in tumor cells with such molecular biological characteristics of BC as the expression of estrogen (ER) and progesterone (PR) receptors (r = -0.53 and r = -0.61, respectively), as well as tumor cells proliferative activity (r = 0.57 and r = 0.49, respectively). The overall 5-year survival of BC patients was found out to be significantly shorter in patients with lactoferrin expression, lack of ER and PR expression and high proliferative potential of tumor cells. Conclusions: the obtained data deepened current knowledge about the association of disorders of iron-binding proteins metabolism in tumor cells and the patients’ body with the malignancy degree of breast cancer; it points to the possibility of applying lactoferrin level in serum and tumor cells to integrated assessment and in-depth characterization of the malignant process in the breast.

References

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: a cancer journal for clinicians 2021; 71 (3): 209–49.

Cancer in Ukraine, 2019–2020. Incidence, mortality, activities of oncological service. Bull Nat Cancer Registry Ukr, № 22, Кyiv, 2020. 82 p.

Smolanka II, Aksenov AA, Aksenova EG, et al. Features of diagnosis and surgical treatment of intraductal neoplasms of the breast. UMJ 2019; 2 (1): 50–3 (in Ukrainian).

Litvinenko ОО, Tatskyi OF. Effective prevention of breast cancer recurrence: the role of exogenous peptides MHP in restoring immune homeostasis. J Klinichna immunolohiia. Alerholohiia. Infektolohiia 2017; 3: 50–7 (in Ukrainian).

DeSantis CE, Miller KD, Goding Sauer A, et al. Cancer statistics for African Americans, 2019. CA: A Cancer Journal for Clinicians 2019; 69 (3): 211–33.

Coleman MP, Quaresma M, Berrino F, et al. Cancer survival in five continents: a worldwide population-based study (CONCORD). Lancet Oncol 2008; 9 (8): 730–56.

Taplin SH, Ichikawa L, Yood MU, et al. Reason for late-stage breast cancer: absence of screening or detection, or breakdown in follow-up? JNCI 2004; 96 (20): 1518–27.

Testa U, Castelli G, Pelosi E. Breast cancer: a molecularly heterogenous disease needing subtype-specific treatments. Medical sciences (Basel, Switzerland) 2020; 8 (1): 18 (https://doi.org/10.3390/medsci8010018).

Laptiev SA, Korzhenevskaia MA, Imyanitov EN. Molecular-genetic «portrait» of breast cancer. The Scientific Notes of IPP-SPSMU 2017; 24 (2): 12–22 (in Russian).

Jung M, Mertens C, Tomat E, et al. Iron as a central player and promising target in cancer progression. Int J Mol Sc 2019; 20 (2): 273.

Chekhun VF, Yalovenko TN, Pavlova AA, et al. The clinical significance of the level of metal-containing proteins in the blood serum of patients with breast cancer. Oncological Journal (Republic of Belarus) 2016; 2 (38): 7–13.

Torti SV, Torti FM. Iron: the cancer connection. Mol Asp Med 2020; 75: 100860.

Nakamura T, Naguro I, Ichijo H. Iron homeostasis and iron-regulated ROS in cell death, senescence and human diseases. BBA 2019; 1863 (9): 1398–1409.

Muhoberac BB, Vidal R. Iron, ferritin, hereditary ferritinopathy, and neurodegeneration. Front Neurosci 2019; 13: 1195.

Gkouvatsos K, Papanikolaou G, Pantopoulos K. Regulation of iron transport and the role of transferrin. BB 2012; 1820 (3): 188–202.

Hagag AA, Badraia IM, Abdelmageed MM, et al. Prognostic value of transferrin receptor-1 (CD71) expression in acute lymphoblastic leukemia. Endocr Metab Immune Disord Drug Targets 2018; 18 (6): 610–17.

Sabra S, Agwa MM. Lactoferrin, a unique molecule with diverse therapeutical and nanotechnological applications. Int J Biol Macromol 2020; 164: 1046–60.

Rodrigues L, Teixeira J, Schmitt F, et al. Lactoferrin and cancer disease prevention. Crit Rev Food Sci Nutr 2008; 49 (3): 203–17.

Zhang Y, Lima CF, Rodrigues LR. Anticancer effects of lactoferrin: Underlying mechanisms and future trends in cancer therapy. Nutr Rev 2014; 72 (12): 763–73.

Tsuda H, Kozu T, Iinuma G, et al. Cancer prevention by bovine lactoferrin: from animal studies to human trial. Biometals 2010; 23 (3): 399–409.

Suzuki YA, Lönnerdal B. Baculovirus expression of mouse lactoferrin receptor and tissue distribution in the mouse. Biome­tals 2004; 17 (3): 301–9.

Duarte DC, Nicolau A, Teixeira JA, et al. The effect of bovine milk lactoferrin on human breast cancer cell lines. J Dairy Sci 2011; 94 (1): 66–76.

Guedes JP, Pereira CS, Rodrigues LR, et al. Bovine milk lactoferrin selectively kills highly metastatic prostate cancer PC-3 and osteosarcoma MG-63 cells in vitro. Front Oncol 2018; 8: 200.

Hu L, Gao CH, Hong C, et al. Expression, purification, and breast cancer cell inhibiting effect of recombinant human lactoferrin C-lobe. Biosci Biotechnol Biochemi 2016; 80 (2): 257–63.

Hwang SM, Chung IY, Jo JH, et al. Comparison of proliferative effect of human lactoferrin and its proteolytic peptide on normal and transformed epithelial cells. Biotechnol. Appl. Biochem 2016; 178 (1): 44–57.

Sobin LH, Wittekind C. TNM. Classification of malignant tumors. Sixth Edition. UICC, Ed Willey-Liss 2003; p. 193.

Lakhani S, Ellis I, Schnitt S, et al. 4th. WHO Classification of Tumours of the Breast. Lyon: IARC Press; 2012.

Budwit-Novotny DA, McCarty KS, Cox EB, et al. Immunohistochemical analyses of estrogen receptor in endometrial adenocarcinoma using a monoclonal antibody. Cancer Res 1986; 46 (10): 5419–25.

Schulz DM, Böllner C, Thomas G, et al. Identification of differentially expressed proteins in triple-negative breast carcinomas using DIGE and mass spectrometry. J Proteome Res 2009; 8 (7): 3430–8.

Rossiello R, Carriero MV, Giordano GG. Distribution of ferritin, transferrin and lactoferrin in breast carcinoma tissue. J Clin Path 1984; 37 (1): 51–5.

Teng CT, Gladwell W, Beard C, et al. Lactoferrin gene expression is estrogen responsive in human and rhesus monkey endometrium. Mol Human Reproduction 2002; 8 (1): 58–67.

Ha NH, Nair VS, Reddy DNS, et al. Lactoferrin–endothelin-1 axis contributes to the development and invasiveness of triple-negative breast cancer phenotypes. Cancer Res 2011; 71 (23), 7259–69.

Published

2021-07-01

How to Cite

Sobchenko, S., Lukianova , N., Bazas, V., Zadvorny , T., Kliusov О., & Chekhun , V. (2021). RELATION BETWEEN LACTOFERRIN LEVELS AND MOLECULAR BIOLOGICAL FEATURES OF BREAST MALIGNANT TUMORS. Oncology, 23(1-2), 33–39. https://doi.org/10.32471/oncology.2663-7928.t-23-1-2021-g.9456

Issue

Section

Original investigations