Skip to main content
Log in

Does Lactoferrin Behave as an Immunohistochemical Oncofetal Marker in Bone and Cartilage Human Neoplasms?

  • Research
  • Published:
Pathology & Oncology Research

Abstract

By immunohistochemistry, lactoferrin (LF) has been extensively investigated in human neoplastic tissues; moreover, LF is able to promote bone growth in a murine model. Until now, no systematic studies on human osteocartilagineous fetal samples have been performed in comparison to corresponding neoplastic specimens to verify if LF may represent an oncofetal marker in this field of pathology. By a monoclonal antibody (clone 1A1; Biodesign International; w.d. 1:75) the distribution pattern of LF in bones of 25 human fetal tissues (8–34 gestation weeks), 10 adults (47–82 years) and 30 cartilage as well as 27 bone tumours (9–76 years) was analyzed. LF was encountered in 23/57 cases of osteocartilagineous tumors and namely in 10/10 giant cell tumours, 5/7 osteoid osteomas, 3/3 chondroblastomas, 3/3 chondromyxoid fibromas, 1/1 myeloma, 1/1 adamantinoma. No LF immunoexpression was detected in osteosarcomas, chondrosarcomas, ossifying fibromas, osteochondroma and enchondromas. In embryo-fetal tissues, LF immunoreactivity was localized in mesenchymal cells as well as in chondroblasts at the 8th gestational week and in immature osteocytes and osteoblasts up to the 18th gestation week, with a considerable decrease by the 24th week. No LF expression was found in any bone district since the 30th and up to the 34th week of gestation as well as in corresponding adult samples. Our findings indicate a role for LF as a bone growth regulator in the early phases of the human endochondral ossification, although the hypothesis of LF as oncofetal marker appears questionable in bone tumours.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. de Lellis RA, Wolfe HJ (1981) The pathobiology of the human calcitonin (C)-cell: a review. Pathol Annu 16(Pt 2):25–52

    PubMed  Google Scholar 

  2. Herberman RB (1977) Immunogenicity of tumor antigens. Biochim Biophys Acta 473(2):93–119

    PubMed  CAS  Google Scholar 

  3. Sarandakou A, Protonotariou E, Rizos D (2007) Tumor markers in biological fluids associated with pregnancy. Crit Rev Clin Lab Sci 44(2):151–178

    Article  PubMed  CAS  Google Scholar 

  4. Monk M, Holding C (2001) Human embryonic genes re-expressed in cancer cells. Oncogene 20(56):8085–8091

    Article  PubMed  CAS  Google Scholar 

  5. Müeller-Pillasch F, Lacher U, Wallrapp C et al (1997) Cloning of a gene highly overexpressed in cancer coding for a novel KH-domain containing protein. Oncogene 14(22):2729–2733

    Article  PubMed  Google Scholar 

  6. Jiang Z, Lohse CM, Chu PG et al (2008) Oncofetal protein IMP3: a novel molecular marker that predicts metastasis of papillary and chromophobe renal cell carcinomas. Cancer 112(12):2676–2682

    Article  PubMed  Google Scholar 

  7. Ward PP, Mendoza-Meneses M, Mulac-Jericevic B et al (1999) Restricted spatiotemporal expression of lactoferrin during murine embryonic development. Endocrinology 140:1852–1860

    Article  PubMed  CAS  Google Scholar 

  8. Cornish J, Callon KE, Naot D et al (2004) Lactoferrin is a potent regulator of bone cell activity and increases bone formation in vivo. Endocrinology 145:366–374

    Article  Google Scholar 

  9. Cornish J, Palmano K, Callon KE et al (2006) Lactoferrin and bone; structureactivity relationships. Biochem Cell Biol 84:297–302

    Article  PubMed  CAS  Google Scholar 

  10. Naot D, Grey A, Reid IR et al (2005) Lactoferrin—a novel bone growth factor. Clin Med Res 3:93–101

    Article  PubMed  Google Scholar 

  11. Giuffrè G, Barresi V, Skliros C et al (2007) Immunoexpression of lactoferrin in human sporadic renal cell carcinomas. Oncol Rep 17:1021–1026

    PubMed  Google Scholar 

  12. Baker EN, Baker HM, Kidd RD (2002) Lactoferrin and transferrin: functional variations on a common structural framework. Biochem Cell Biol 80(1):27–34

    Article  PubMed  CAS  Google Scholar 

  13. Masson PL, Heremans JF (1971) Lactoferrin in milk from different species. Comp Biochem Physiol B 39(1):119–129

    Article  PubMed  CAS  Google Scholar 

  14. Lönnerdal B (2009) Nutritional roles of lactoferrin. Curr Opin Clin Nutr Metab Care 12(3):293–297

    Article  PubMed  Google Scholar 

  15. Pierce A, Legrand D, Mazurier J (2009) Lactoferrin: a multifunctional protein. Med Sci 25(4):361–369

    Google Scholar 

  16. Rodrigues L, Teixeira J, Schmitt F et al (2009) Lactoferrin and cancer disease prevention. Crit Rev Food Sci Nutr Mar 49(3):203–217

    Article  CAS  Google Scholar 

  17. Benaïssa M, Peyrat JP, Hornez L et al (2005) Expression and prognostic value of lactoferrin mRNA isoforms in human breast cancer. Int J Cancer 114(2):299–306

    Article  PubMed  Google Scholar 

  18. Wolf JS, Li D, Taylor RJ, O'Malley BW Jr (2003) Lactoferrin inhibits growth of malignant tumors of the head and neck. ORL J Otorhinolaryngol Relat Spec 65(5):245–249

    Article  PubMed  CAS  Google Scholar 

  19. Xiao Y, Monitto CL, Minhas KM et al (2004) Lactoferrin down-regulates G1 cyclin-dependent kinases during growth arrest of head and neck cancer cells. Clin Cancer Res 10(24):8683–8686

    Article  PubMed  CAS  Google Scholar 

  20. Caselitz J, Jaup T, Seifert G (1981) Lactoferrin and lysozyme in carcinomas of the parotid gland. A comparative immunocytochemical study with the occurrence in normal and inflamed tissue. Virchows Arch A Pathol Anat Histol 394(1–2):61–73

    Article  PubMed  CAS  Google Scholar 

  21. Barresi G, Tuccari G (1984) Lactoferrin in benign hypertrophy and carcinomas of the prostatic gland. Virchows Arch A Pathol Anat Histopathol 403:59–66

    Article  PubMed  CAS  Google Scholar 

  22. Charpin C, Lachard A, Pourreau-Schneider N et al (1985) Localization of lactoferrin and nonspecific cross-reacting antigen in human breast carcinomas. An immunohistochemical study using the avidin-biotin-peroxidase complex method. Cancer 55(11):2612–2617

    Article  PubMed  CAS  Google Scholar 

  23. Rossiello R, Carriero MV, Giordano GG (1984) Distribution of ferritin, transferrin and lactoferrin in breast carcinoma tissue. J Clin Pathol 37(1):51–55

    Article  PubMed  CAS  Google Scholar 

  24. Barresi G, Tuccari G (1987) Iron-binding proteins in thyroid tumours. An immunocytochemical study Pathol Res Pract 182(3):344–351

    CAS  Google Scholar 

  25. Cabaret V, Vilain MO, Delobelle-Deroide A et al (1992) Immunohistochemical demonstration of ceruloplasmin and lactoferrin in a series of 59 thyroid tumors. Ann Pathol 12(6):347–352

    PubMed  CAS  Google Scholar 

  26. Tuccari G, Barresi G (1985) Immunohistochemical demonstration of lactoferrin in follicular adenomas and thyroid carcinomas. Virchows Arch A Pathol Anat Histopathol 406:67–74

    Article  PubMed  CAS  Google Scholar 

  27. Tuccari G, Barresi G, Arena F et al (1989) Immunocytochemical detection of lactoferrin in human gastric carcinomas and adenomas. Arch Pathol Lab Med 113:912–915

    PubMed  CAS  Google Scholar 

  28. Tuccari G, Rizzo A, Crisafulli C et al (1992) Iron-binding proteins in human colorectal adenomas and carcinomas: an immunocytochemical investigation. Histol Histopathol 7:543–547

    PubMed  CAS  Google Scholar 

  29. Tuccari G, Rossiello R, Barresi G (1997) Iron binding proteins in gallbladder carcinomas. An immunocytochemical investigation. Histol Histopathol 12:671–676

    PubMed  CAS  Google Scholar 

  30. Tuccari G, Giuffrè G, Crisafulli C et al (1999) Immunohistochemical detection of lactoferrin in human astrocytomas and multiforme glioblastomas. Eur J Histochem 43(4):317–322

    PubMed  CAS  Google Scholar 

  31. Tuccari G, Giuffrè G, Scarf R et al (2005) Immunolocalization of lactoferrin in surgically resected pigmented skin lesions. Eur J Histochem 49(1):33–38

    PubMed  CAS  Google Scholar 

  32. Giuffrè G, Arena F, Scarfì R et al (2006) 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(2):257–263

    PubMed  Google Scholar 

  33. Ieni A, Barresi V, Grosso M et al (2009) Lactoferrin immuno-expression in human normal and neoplastic bone tissue. J Bone Miner Metab 27:364–371

    Article  PubMed  CAS  Google Scholar 

  34. Ieni A, Barresi V, Grosso M et al (2009) Immunolocalization of lactoferrin in cartilageforming neoplasms. J Orthop Sci 14:732–737

    Article  PubMed  CAS  Google Scholar 

  35. Garré C, Bianchi-Scarrá G, Sirito M et al (1992) Lactoferrin binding sites and nuclear localization in K562(S) cells. J Cell Physiol 153(3):477–482

    Article  PubMed  Google Scholar 

  36. Penco S, Scarfi S, Giovine M et al (2001) Identification of an import signal for, and the nuclear localization of, human lactoferrin. Biotechnol Appl Biochem 34:151–159

    Article  PubMed  CAS  Google Scholar 

  37. James IE, Dodds RA, Olivera DL et al (1996) Human osteoclastoma-derived stromal cells: correlation of the ability to form mineralized nodules in vitro with formation of bone in vivo. J Bone Miner Res 11(10):1453–1460

    Article  PubMed  CAS  Google Scholar 

  38. Joyner CJ, Quinn JM, Triffitt JT et al (1992) Phenotypic characterisation of mononuclear and multinucleated cells of giant cell tumour of bone. Bone Miner 16(1):37–48

    Article  PubMed  CAS  Google Scholar 

  39. Pittenger MF, Mackay AM, Beck SC et al (1999) Multilineage potential of adult human mesenchymal stem cells. Science 284(5411):143–147

    Article  PubMed  CAS  Google Scholar 

  40. Karsenty G (2008) Transcriptional control of skeletogenesis. Annu Rev Genomics Hum Genet 9:183–196

    Article  PubMed  CAS  Google Scholar 

  41. Wülling M, Delling G, Kaiser E (2003) The origin of the neoplastic stromal cell in giant cell tumor of bone. Hum Pathol 34(10):983–993

    Article  PubMed  Google Scholar 

  42. Aigner T (2007) Histogenesis of the skeleton and morphogenesis of cartilage-forming neoplasias. Verh Dtsch Ges Pathol 91:49–56

    PubMed  CAS  Google Scholar 

  43. Yagi M, Suzuki N, Takayama T (2009) Effects of lactoferrin on the differentiation of pluripotent mesenchymal cells. Cell Biol Int 33(3):283–289

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Antonio Ieni.

Additional information

Presented in part at the 22nd European Congress of Pathology, 4–9 September 2009—Florence (Italy)

Rights and permissions

Reprints and permissions

About this article

Cite this article

Ieni, A., Barresi, V., Grosso, M. et al. Does Lactoferrin Behave as an Immunohistochemical Oncofetal Marker in Bone and Cartilage Human Neoplasms?. Pathol. Oncol. Res. 17, 287–293 (2011). https://doi.org/10.1007/s12253-010-9311-5

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12253-010-9311-5

Keywords

Navigation