Immunoexpression of lactoferrin in bone metastases and corresponding primary carcinomas

Ieni,A.; Barresi,V.; Branca,G.; Giuffrè,G.; Rosa,M. A.; Tuccari,G.

doi:10.3892/ol.2013.1227

Immunoexpression of lactoferrin in bone metastases and corresponding primary carcinomas

Authors:
- A. Ieni
- V. Barresi
- G. Branca
- G. Giuffrè
- M. A. Rosa
- G. Tuccari
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Affiliations: Department of Human Pathology, Section of Pathological Anatomy, University of Messina, Messina, Italy, Department of Surgical Specialties, Section of Oncological Orthopaedics, University of Messina, Messina, Italy
Published online on: March 5, 2013 https://doi.org/10.3892/ol.2013.1227
Pages: 1536-1540

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Abstract

Although the immunohistochemical presence of lactoferrin (LF) in pathological neoplastic bone and cartilage samples has previously been studied, no data concerning the distribution of LF in bone metastases of cancers that have originated from different organs are available at present. Consequently, using a monoclonal antibody, we have investigated the immunohistochemical LF pattern in 50 formalin-fixed and paraffin-embedded samples of human bone metastases and their corresponding primary carcinoma tumours (breast, 8; prostate, 4; kidney, 4; lung, 3; colon-rectum, 2 and uterus, 4). Quantification of LF immunoreactivity was performed using an intensity distribution (ID) score. LF immunostaining with a variable ID score was encountered in 11/25 (44%) metastatic lesions. In particular, the LF immunoreactivity was identified with a percentage ranging from 50 to 75% of bone metastases due to prostatic, renal, uterine and colorectal carcinomas; the positivity decreased in breast carcinomas (37.5%) and was completely absent in lung cancers. No differences in the LF-ID score were observed between primary and metastatic neoplastic localisations. Additionally, no correlations were identified between LF immunoexpression and the other parameters tested, including the age and gender of patients. Regardless of the mechanism of action of LF in human malignant tumours, we identified LF immunohistochemical reproducibility at primary and metastatic sites. Therefore, we hypothesise that the presence of LF in native neoplastic carcinomatous clones is maintained in secondary bone metastatic deposits.

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1	González-Chávez SA, Arévalo-Gallegos S and Rascón-Cruz Q: Lactoferrin: structure, function and applications. Int J Antimicrob Agents. 33:301.e1–e.8. 2009.
2	Steijns JM and van Hooijdonk AC: Occurrence, structure, biochemical properties and technological characteristics of lactoferrin. Br J Nutr. 84(Suppl 1): S11–S17. 2000. View Article : Google Scholar : PubMed/NCBI
3	van der Strate BW, Beljaars L, Molema G, Harmsen MC and Meijer DK: Antiviral activities of lactoferrin. Antiviral Res. 52:225–239. 2001.
4	Öztaş Yeşim ER and Özgüneş N: Lactoferrin: a multifunctional protein. Adv Mol Med. 1:149–154. 2005.
5	Pierce A, Legrand D and Mazurier J: Lactoferrin: a multifunctional protein. Med Sci. 25:361–369. 2009.
6	de Mejia EG and Dia VP: The role of nutraceutical proteins and peptides in apoptosis, angiogenesis, and metastasis of cancer cells. Cancer Metastasis Rev. 29:511–528. 2010.PubMed/NCBI
7	Mason DY and Taylor CR: Distribution of transferrin, ferritin, and lactoferrin in human tissues. J Clin Pathol. 31:316–327. 1978. View Article : Google Scholar : PubMed/NCBI
8	Reitamo S, Konttinen YT, Dodd S and Adinolfi M: Distribution of lactoferrin in human fetal tissues. Acta Paediatr Scand. 70:395–398. 1981. View Article : Google Scholar : PubMed/NCBI
9	Ieni A, Barresi V, Grosso M and Tuccari G: Immunohistochemical evidence of lactoferrin in human embryo-fetal bone and cartilage tissues. Cell Biol Int. 34:845–849. 2010. View Article : Google Scholar : PubMed/NCBI
10	Cornish J: Lactoferrin promotes bone growth. Biometals. 17:331–335. 2004. View Article : Google Scholar : PubMed/NCBI
11	Naot D, Grey A, Reid IR and Cornish J: Lactoferrin a novel bone growth factor. Clin Med Res. 3:93–101. 2005. View Article : Google Scholar : PubMed/NCBI
12	Cornish J and Naot D: Lactoferrin as an effector molecule in the skeleton. Biometals. 23:425–430. 2010. View Article : Google Scholar : PubMed/NCBI
13	Ieni A, Barresi V, Grosso M, Rosa MA and Tuccari G: Lactoferrin immuno-expression in human normal and neoplastic bone tissue. J Bone Miner Metab. 27:364–371. 2009. View Article : Google Scholar : PubMed/NCBI
14	Ieni A, Barresi V, Grosso M, Rosa MA and Tuccari G: Immunolocalization of lactoferrin in cartilage-forming neoplasms. J Orthop Sci. 14:732–737. 2009. View Article : Google Scholar : PubMed/NCBI
15	Ieni A, Barresi V, Grosso M, Speciale G, Rosa MA and Tuccari G: Does lactoferrin behave as an immunohistochemical oncofetal marker in bone and cartilage human neoplasms? Pathol Oncol Res. 17:287–293. 2011. View Article : Google Scholar : PubMed/NCBI
16	Tuccari G, Villari D, Giuffrè G, Simone A, Squadrito G, Raimondo G and Barresi G: Immunohistochemical evidence of lactoferrin in hepatic biopsies of patients with viral or cryptogenetic chronic liver disease. Histol Histopathol. 17:1077–1083. 2002.PubMed/NCBI
17	Blais A, Malet A, Mikogami T, Martin-Rouas C and Tomé D: Oral bovine lactoferrin improves bone status of ovariectomized mice. Am J Physiol Endocrinol Metab. 296:1281–1288. 2009. View Article : Google Scholar : PubMed/NCBI
18	Guo HY, Jiang L, Ibrahim SA, Zhang L, Zhang H, Zhang M and Ren FZ: Orally administered lactoferrin preserves bone mass and microarchitecture in ovariectomized rats. J Nutr. 139:958–964. 2009. View Article : Google Scholar : PubMed/NCBI
19	Takayama Y and Mizumachi K: Effect of lactoferrin-embedded collagen membrane on osteogenic differentiation of human osteoblast-like cells. J Biosci Bioeng. 107:191–195. 2009. View Article : Google Scholar : PubMed/NCBI
20	Naot D, Chhana A, Matthews BG, Callon KE, Tong PC, Lin JM, Costa JL, Watson M, Grey AB and Cornish J: Molecular mechanisms involved in the mitogenic effect of lactoferrin in osteoblasts. Bone. 49:217–224. 2011. View Article : Google Scholar : PubMed/NCBI
21	Tuccari G and Barresi G: Lactoferrin in human tumours: immunohistochemical investigations during more than 25 years. Biometals. 24:775–784. 2011.PubMed/NCBI
22	Penco S, Scarfì S and Giovine M: Identification of an import signal for, and the nuclear localization of, human lactoferrin. Biotechnol Appl Biochem. 34:151–159. 2001. View Article : Google Scholar : PubMed/NCBI
23	Barresi G and Tuccari G: Lactoferrin in benign hypertrophy and carcinomas of the prostatic gland. Virchows Arch A Pathol Anat Histopathol. 403:59–66. 1984. View Article : Google Scholar : PubMed/NCBI
24	Tuccari G, Rizzo A, Crisafulli C and Barresi G: Iron-binding proteins in human colorectal adenomas and carcinomas: an immunocytochemical investigation. Histol Histopathol. 7:543–547. 1992.PubMed/NCBI
25	Giuffrè G, Arena F, Scarfì R, Simone A, Todaro P and Tuccari G: Lactoferrin immunoexpression in endometrial carcinomas: relationships with sex steroid hormone receptors (ER and PR), proliferation indices (Ki-67 and AgNOR) and survival. Oncol Rep. 16:257–263. 2006.PubMed/NCBI
26	Giuffrè G, Barresi V, Skliros C, Barresi G and Tuccari G: Immunoexpression of lactoferrin in human sporadic renal cell carcinomas. Oncol Rep. 17:1021–1026. 2007.PubMed/NCBI
27	Wurster K, Heberling D and Rapp W: Carcinoembryogenic antigen (CEA) and lactoferrin (LF) in benign and malignant disease of the breast. A contribution to the immuno-histological demonstration of marker substances. Geburtshilfe Frauenheilkd. 40:412–422. 1980.(In German).
28	Charpin C, Lachard A, Pourreau-Schneider N, et al: Localization of lactoferrin and nonspecific cross-reacting antigen in human breast carcinomas. An immunohistochemical study using the avidin-biotin-peroxidase complex method. Cancer. 55:2612–2617. 1985. View Article : Google Scholar
29	Wrba F, Reiner A, Markis-Ritzinger E, Holzner JH, Reiner G and Spona J: Prognostic significance of immunohistochemical parameters in breast carcinomas. Pathol Res Pract. 183:277–283. 1988. View Article : Google Scholar : PubMed/NCBI
30	Caselitz J, Jaup T and Seifert G: Lactoferrin and lysozyme in carcinomas of the parotid gland. Virchows Arch A Pathol Anat Histol. 394:61–73. 1981. View Article : Google Scholar : PubMed/NCBI
31	Cabaret V, Vilain MO, Delobelle-Deroide A and Vanseymortier L: Immunohistochemical demonstration of ceruloplasmin and lactoferrin in a series of 59 thyroid tumors. Ann Pathol. 12:347–352. 1992.(In French).
32	Weinberg ED: Iron withholding: a defense against infection and neoplasia. Physiol Rev. 64:65–102. 1984.PubMed/NCBI
33	Ye XY, Wang HX, Liu F and Ng TB: Ribonuclease, cell-free translation-inhibitory and superoxide radical scavenging activities of the iron-binding protein lactoferrin from bovine milk. Int J Biochem Cell Biol. 32:235–241. 2000. View Article : Google Scholar : PubMed/NCBI
34	Tuccari G, Rossiello R and Barresi G: Iron binding proteins in gallbladder carcinomas. An immunocytochemical investigation. Histol Histopathol. 12:671–676. 1997.PubMed/NCBI
35	Tuccari G, Giuffrè G, Scarf R, Simone A, Todaro P and Barresi G: Immunolocalization of lactoferrin in surgically resected pigmented skin lesions. Eur J Histochem. 49:33–38. 2005. View Article : Google Scholar : PubMed/NCBI
36	Roiron D, Amouric M, Marvaldi J and Figarella C: Lactoferrin-binding sites at the syurface of HT29-D4 cells. Comparison with transferrin. Eur J Biochem. 186:367–373. 1989. View Article : Google Scholar : PubMed/NCBI
37	Suzuki YA, Lopez V and Lönnerdal B: Mammalian lactoferrin receptors: structure and function. Cell Mol Life Sci. 62:2560–2575. 2005. View Article : Google Scholar : PubMed/NCBI
38	Ward PP, Paz E and Conneely OM: Multifunctional roles of lactoferrin: a critical overview. Cell Mol Life Sci. 62:2540–2548. 2005. View Article : Google Scholar : PubMed/NCBI
39	Rodrigues L, Teixeira J, Schmitt F, Paulsson M and Månsson HL: Lactoferrin and cancer disease prevention. Crit Rev Food Sci Nutr. 49:203–217. 2009. View Article : Google Scholar : PubMed/NCBI
40	Fujita K, Matsuda E, Sekine K, Iigo M and Tsuda H: Lactoferrin enhances Fas expression and apoptosis in the colon muciosa of azoxymethane-treated rats. Carcinogenesis. 25:1961–1966. 2004. View Article : Google Scholar : PubMed/NCBI
41	Norrby K: Human apo-lactoferrin enhances angiogenesis mediated by vascular endothelial growth factor A in vivo. J Vasc Res. 41:293–304. 2004. View Article : Google Scholar : PubMed/NCBI
42	Shimamura M, Yamamoto Y, Ashino H, Oikawa T, Hazato T, Tsuda H and Iigo M: Bovine lactoferrin inhibits tumor induced angiogenesis. Int J Cancer. 111:111–116. 2004. View Article : Google Scholar : PubMed/NCBI
43	Damiens E, El Yazidi I, Mazurier J, et al: Lactoferrin inhibits G1 cyclin-dependent kinases during growth arrest of human breast carcinoma cells. J Cell Biochem. 74:486–498. 1999. View Article : Google Scholar : PubMed/NCBI
44	Xiao Y, Monitto CL, Minhas KM and Sidransky D: Lactoferrin down-regulates G1 cyclin-dependent kinases during growth arrest of head and neck cancer cells. Clin Cancer Res. 10:8683–8686. 2004. View Article : Google Scholar : PubMed/NCBI