Skip to main content
SpringerLink
Log in

Naturally-occurring porphyrins in a spontaneous-tumour bearing mouse model

  • Paper
  • Published:
Photochemical & Photobiological Sciences Aims and scope Submit manuscript

Abstract

An increase in naturally-occurring porphyrins has been described in the blood of subjects bearing different kinds of tumours, that has been proposed as an additional parameter for the diagnosis of occult cancer, although at present the reason for the phenomenon is not exactly defined. In this work the increase of porphyrins in plasma of tumour-bearing subjects has been investigated in parallel with their occurrence in other tissues, considering the systemic iron homeostasis subversion taking place in the presence of cancer. The transgenic female MMTV-neu mouse-developing spontaneous mammary adenocarcinoma has been used as an experimental model, in comparison to non-transgenic C1 mouse as a control. The spleen, accomplishing both hemocatheretic and hemopoietic functions in rodents, and the liver have been considered because of their deep engagement in heme metabolism, entailing both the fate of protoporphyrin IX (PpIX) as its ultimate precursor, and iron homeostasis. Investigations have been performed by means of microspectrofluorometric and image analysis of tissue autofluorescence (AF), and histochemical detection of non-heme iron. In tumour-bearing mouse, along with a marked PpIX presence in tumour, a PpIX enhancement in spleen and liver is observed, that is accompanied by a significant increase in plasma. The phenomenon can be related to a systemic alteration of heme metabolism induced by tumour cells to face their survival and proliferation requirements.

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

Access this article

Log in via an institution

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

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. G. A. Wagnières, W. M. Star and B. C. Wilson, In vivo fluorescence spectroscopy and imaging for oncological applications, Photochem. Photobiol., 1998, 68, 603–632.

    Article  PubMed  Google Scholar 

  2. N. Ramanujam, Fluorescence spectroscopy of neoplastic and nonneoplastic tissues, Neoplasia, 2000, 2, 89–117.

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. N. Ramanujam, Fluorescence spectroscopy in vivo, in Encyclopedia of Analytical Chemistry, ed. R. A. Meyers, Chichester, John Wiley & Sons Ltd, Madison, 2000, pp. 1–37.

    Google Scholar 

  4. R. Da Costa, H. Andersson and B. C. Wilson, Molecular fluorescence excitation-emission matrices relevant to tissue spectroscopy, Photochem. Photobiol., 2003, 78, 384–392.

    Article  Google Scholar 

  5. G. Bottiroli and A. C. Croce, The autofluorescence spectroscopy of cells and tissue as a tool for biomedical diagnosis, in Comprehensive Series in Photosciences Lasers and Current Optical Techniques in Biology, ed. G. Palumbo and R. Pratesi, RSC Books and Databases, Cambridge, 2004, pp. 189–210.

    Google Scholar 

  6. A. Policard, Etudes sur les aspects offerts par les tumeurs experimentales examinees a la lumière de Woods, C.R. Soc. Biol., 1924, 91, 1423–1425.

    Google Scholar 

  7. F. N. Ghadially and W. J. P. Neish, Porphyrin fluorescence of experimentally produces squamous cell carcinoma, Nature, 1960, 188, 1124.

  8. G. Bottiroli, A. C. Croce, D. Locatelli, R. Marchesini, E. Pignoli, S. Tomatis, C. Cuzzoni, S. Di Palma, M. Dal Fante and P. Spinelli, Natural fluorescence of normal and neoplastic colon: a comprehensive ex vivo study, Lasers Surg. Med., 1995, 16, 48–60.

    Article  CAS  PubMed  Google Scholar 

  9. K. T. Moesta, B. Ebert, T. Handke, D. Nolte, C. Nowak, W. E. Haensch, R. K. Pandey, T. J. Dougherty, H. Rinneberg and P. M. Schlag, Protoporphyrin IX occurs naturally in colorectal cancers and their metastases, Cancer Res., 2001, 61, 991–999.

    CAS  PubMed  Google Scholar 

  10. B. Mayinger, M. Jordan, P. Horner, C. Gerlach, S. Muehldorfer, B. R. Bittorf, K. E. Matzel, W. Hohenberger, E. Haln and K. Guenter, Endoscopic light-induced autofluorescence spectroscopy for the diagnosis of colorectal cancer and adenoma, J. Photochem. Photobiol., B, 2003, 70, 13–20.

    Article  CAS  Google Scholar 

  11. R. M. Cothren, M. V. Jr Sivak, J. Van Dam, R. E. Petras, M. Fitzmaurice, J. M. Crawford, J. Wu, J. F. Brennan, R. P. Rava, R. Manoharan and M. S Feld, Detection of dysplasia at colonoscopy using laser-induced fluorescence: a blinded study, Gastrointest. Endosc., 1996, 44, 168–176.

    Article  CAS  PubMed  Google Scholar 

  12. K. Nakanishi, Y. Ohsakia, M. Kuriharab, S. Nakaoa, Y. Fujita, K. Takeyamac, S. Osanaia, N. Miyokawad and S. Nakajima, Color autofluorescence from cancer lesions: Improved detection of central type lung cancer, Lung Cancer, 2007, 58, 214–219.

    Article  PubMed  Google Scholar 

  13. D. M. Harris and J. Werkhaven, Endogenous porphyrin fluorescence in tumours., Lasers Surg. Med., 1987, 7, 467–472.

    Article  CAS  PubMed  Google Scholar 

  14. K. Koeing and H. Schneckenburger, Laser-induced autofluorescence for medical diagnosis, J. Fluoresc., 1994, 4, 17–37.

    Article  Google Scholar 

  15. L. Leibovici, N. Schoenfeld, H. A. Yehoshua, R. Mamet, E. Rakowsky, A. Shindel and A. Atsmon, Activity of porphobilinogen deaminase in peripheral blood mononuclear cells of patients with metastatic cancer, Cancer, 1988, 62, 2297–2300.

    Article  CAS  PubMed  Google Scholar 

  16. N. Schoenfeld, O. Epstein, M. Lahav, R. Mamet, M. Shaklai and A. Atsmon, The heme biosynthetic pathway in lymphocytes of patients with malignant lymphoproliferative disorders, Cancer Lett., 1988, 43, 43–48.

    Article  CAS  PubMed  Google Scholar 

  17. Q. Peng, T. Warloe, K. Berg, J. Moan, M. Kongshaug, K. E. Giercksky and J. M. Nesland, 5-Aminolevulinic acid-based photodynamic therapy. Clinical research and future challenges, Cancer, 1997, 79, 2282–2308.

    Article  CAS  PubMed  Google Scholar 

  18. X. Xu, J. Meng and S. Hou, The characteristic fluorescence of the serum of cancer patients, J. Lumin., 1988, 40–41, 219–220.

    Article  Google Scholar 

  19. S. Madhuri, N. Vengadesan, P. Aruna, D. Koteeswaran, P. Venkatesan and S. Ganesan, Native fluorescence spectroscopy of blood plasma in the characterization of oral malignance, Photochem. Photobiol., 2003, 78, 197–204.

    Article  CAS  PubMed  Google Scholar 

  20. V. Masilamani, K. Al-Zhrani, M. Al-Salhi, A. Al-Diab and M. Al-Ageily, Cancer diagnosis by autofluorescence of blood components, J. Lumin., 2004, 109, 143–154.

    CAS  Google Scholar 

  21. L. C. Courrol, F. R. De, Oliveira Silva, E. L. Coutinho, M. F. Piccoli, R. D. Mansano, N. D. Vieira Júnior, N. Schor and M. H. Bellini, Study of blood porphyrin spectral profile for diagnosis of tumour progression, J. Fluoresc., 2007, 17, 289–292.

    Article  CAS  PubMed  Google Scholar 

  22. B. D. Dickerson, B. L. Geist, W. B. Spillman and J. L. Robertson, Canine cancer screening via ultraviolet absorbance, fluorescence spectroscopy of serum proteins, Appl. Opt., 2007, 46, 8080–8088.

    Article  CAS  PubMed  Google Scholar 

  23. M. Lualdi, L. Battaglia, A. Colombo, E. Leo, D. Morelli, E. Poiasina, A. Vannelli and R. Marchesini, Colorectal cancer detection by means of optical fluoroscopy. A study on 494 subjects, Front. Biosci., 2010, E2, 694–700.

    Article  CAS  Google Scholar 

  24. O. S. Wolfbeis and M. Leiner, Mapping of the total fluorescence of human blood serum as a new method for its characterization, Anal. Chim. Acta, 1985, 167, 203–215.

    Article  CAS  Google Scholar 

  25. M. R. Hubbmann, M. J. P. Leiner and R. J. Schaur, Ultraviolet fluorescence of human sera: I. Sources, of characteristic differences in the ultroviolet fluorescence spectra of sera from normal and cancerbearing humans, Clin. Chem., 1990, 36, 1880–1883.

    Article  Google Scholar 

  26. R. Kalaivani, V. Masilamani, K. Sivaji, M. Elangovan, V. Selvaraj, S. G. Balamurugan and M. S. Al-Salhi, Fluorescence spectra of blood components for breast cancer diagnosis, Photomed. Laser Surg., 2008, 26, 251–256.

    Article  CAS  PubMed  Google Scholar 

  27. F. R. de Oliveira Silva, M. H. Bellini, V. R. Tristào, N. Schor, N. D. Vieira Jr and L. C. Courrol, Intrinsic fluorescence of protophorphyrin IX from blood samples can yield information on the growth of prostate tumours, J. Fluoresc., 2010, 20, 1159–1165.

    Article  CAS  Google Scholar 

  28. T. Ganz and E. Nemeth, Hepcidin and Disorders of Iron Metabolism, Annu. Rev. Med., 2011, 62, 347–360.

    Article  CAS  PubMed  Google Scholar 

  29. J. L. Buss, F. M. Torti and S. V. Torti, The role of iron chelation in cancer therapy, Curr. Med. Chem., 2003, 10, 1051–1064.

    Article  Google Scholar 

  30. D. R. Richardson, Iron and neoplasia: serum transferrin receptor and ferritin in prostate cancer, J. Lab. Clin. Med., 2004, 144, 173–175.

    Article  CAS  PubMed  Google Scholar 

  31. I. Freitas, E. Boncompagni, R. Vaccarone, C. Fenoglio, S. Barni and G. F. Baronzio, Iron accumulation in mammary tumour suggests a tug of war between tumour and host for the microelement, Anticancer Res., 2007, 27, 3059–3065.

    CAS  PubMed  Google Scholar 

  32. N. Yanai, Y. Matsuya and M. Obinata, Spleen stromal cell lines selectively support erythroid colony formation, Blood, 1989, 74, 2391–2397.

    Article  CAS  PubMed  Google Scholar 

  33. F. J. M. F. Dor, M. L. Ramirez, K. Parmar, E. L. Altman, C. A. Huang, J. D. Down and D. K. C. Cooper, Primitive hematopoietic cell populations reside in the spleen: Studies in the pig, baboon and human, Exp. Hematol., 2006, 34, 1573–1582.

    Article  CAS  PubMed  Google Scholar 

  34. F. Lucchini, M. G. Sacco, N. Hu, A. Villa, J. Brown, L. Cesano, L. Mangiarini, G. Rindi, S. Kindl, F. Sessa, P. Vezzoni and L. Clerici, Early and multifocal tumors in breast, salivary, harderian and epididymal tissues developed in MMTY-Neu transgenic mice, Cancer Lett., 1992, 64, 203–209.

    Article  CAS  PubMed  Google Scholar 

  35. R. Rotomskis, G. Streckyte and S. Bagdonas, Phototransformations of sensitizers. 2. Photoproducts formed in aqueous solution of porphyrins, J. Photochem. Photobiol., B, 1997, 39, 172–175.

    Article  CAS  Google Scholar 

  36. J. S. Dysart and M. S. Patterson, Photobleaching kinetics, photoproduct formation, and dose estimation during ALA induced PpIX PDT of MLL cells under well oxygenated and hypoxic conditions, Photochem. Photobiol. Sci., 2006, 5, 73–81.

    Article  CAS  PubMed  Google Scholar 

  37. W. Marquardt, An algorithm for least-squares estimation of non-linear parameters, J. Soc. Indust. Appl. Math., 1963, 11, 431–441.

    Article  Google Scholar 

  38. A. C. Croce, A. Ferrigno, M. Vairetti, R. Bertone, I. Freitas and G. Bottiroli, Autofluorescence properties of isolated rat hepatocytes under different metabolic conditions, Photochem. Photobiol. Sci., 2004, 3, 920–926.

    Article  CAS  PubMed  Google Scholar 

  39. G. Weagle, P. E. Paterson, J. Kennedy and R. Pottier, The nature of the chromophore responsible for naturally occurring fluorescence in mouse skin, J. Photochem. Photobiol., B, 1988, 2, 313–320.

    Article  CAS  Google Scholar 

  40. S. Bagdonas, L. W. Ma, V. Iani, R. Rotomskis, P. Juzenas and J. Moan, Phototransformations of 5-animolevulinic Acid-Induced protoporphyrin IX in vitro: A spectroscopic study, Photochem. Photobiol., 2000, 72, 186–192.

    Article  CAS  PubMed  Google Scholar 

  41. E. Nagababu and J. M. Rifkind, Heme degradation by reactive oxygen species, Antioxid. Redox Signal, 2004, 6, 967–978.

    CAS  PubMed  Google Scholar 

  42. G. Bottiroli, R. Ramponi and A. C. Croce, Quantitative analysis of intracellular behaviour of porphyrins, Photochem. Photobiol., 1987, 46, 663–667.

    Article  CAS  PubMed  Google Scholar 

  43. J. Kaczynski, G. Hansson and S. Wallerstedt, Increased porphyrins in primary liver cancer mainly reflect a parallel liver disease, Gastroenterol. Res. Pract., 2009, 2009, 6, DOI: 10.1155/2009/402394.

    Article  Google Scholar 

  44. M. Al-Salhi, V. Masilamani, T. Vijmasi, H. Al-Nachawati and A. P. Vijayaraghavan, Lung Cancer Detection by Native Fluorescence Spectra of Body Fluids-A Preliminary Study, J. Fluoresc., 2010, DOI: 10.1007/s10895-010-0751-9.

    Google Scholar 

  45. S. Taketani, M. Ishigaki, A. Mizutani, M. Uebayashi, M. Numata, Y. Ohgari and S. Kitajima, Heme Synthase (Ferrochelatase) Catalyzes the Removal of Iron from Heme and Demetalation of Metalloporphyrins, Biochemistry, 2007, 46, 15054–15061.

    Article  CAS  PubMed  Google Scholar 

  46. M. Sakaino, M. Ishigaki, Y. Ohgari, S. Kitajima, R. Masaki, A. Yamamoto and S. Taketani, Dual mitochondrial localization and different roles of the reversible reaction of mammalian ferrochelatase, FEBS J., 2009, 276, 5559–5570.

    Article  CAS  PubMed  Google Scholar 

  47. F. Gomes de Go´es Rocha, K. C. Barbosa Chavez, C. Zanini Gomes, C. Barricheli Campanharo, L. Coronato Courrol, N. Schor and M. H. Bellini, Erythrocyte Protoporphyrin Fluorescence as a Biomarker for Monitoring Antiangiogenic Cancer Therapy, J. Fluoresc., 2010, 20, 1225–1231.

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. IGM-CNR, Sezione Istochimica e Citometria, Dipartimento di Biologia Animale, Università di Pavia, 27100, Pavia, Italy

    Anna Cleta Croce, Gerardo Santamaria, Uliana De Simone, Isabel Freitas & Giovanni Bottiroli

  2. Centro Ricerche Biotecnologiche, Università Cattolica del Sacro Cuore, 26100, Cremona, Italy

    Franco Lucchini

Authors
  1. Anna Cleta Croce
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Gerardo Santamaria
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Uliana De Simone
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Franco Lucchini
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Isabel Freitas
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Giovanni Bottiroli
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Giovanni Bottiroli.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Croce, A.C., Santamaria, G., De Simone, U. et al. Naturally-occurring porphyrins in a spontaneous-tumour bearing mouse model. Photochem Photobiol Sci 10, 1189–1195 (2011). https://doi.org/10.1039/c0pp00375a

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1039/c0pp00375a

Search

Navigation