Skip to main content

Advertisement

SpringerLink
Log in

Erythrocyte Protoporphyrin Fluorescence as a Biomarker for Monitoring Antiangiogenic Cancer Therapy

  • Original Paper
  • Published:
Journal of Fluorescence Aims and scope Submit manuscript

Abstract

Renal cell carcinoma (RCC) remains one of the greatest challenges of urological oncology and is the third leading cause of death in genitourinary cancers. RCCs are highly vascularized and are amenable to antiangiogenic therapy. Endostatin (ES) is a fragment of collagen XVIII that possesses antiangiogenic activity. In this study, we examined the potential of erythrocyte PpIX fluorescence spectroscopy for monitoring the efficacy of antiangiogenic therapy in metastatic renal cell carcinoma (mRCC), using an orthotopic metastatic mouse model. Balb/C-bearing Renca cells were treated with NIH/3T3-LendSN cells. Lung weight, nodule area, microvascular area (MVA), and erythrocyte PpIX fluorescence were evaluated. Emission spectra were obtained by exciting the samples at 405 nm. There was a significant decrease in lung wet weight, lung nodule area and MVA in the treated group compared to the control group (P < 0.001). Significant differences in autofluorescence shape were observed in the 620–650 nm spectral region. The most intense fluorescence peak was observed at ∼632 nm. The autofluorescence of the control samples was about 53% higher than that of normal blood (P < 0.05). In the group treated with ES, the autofluorescence was about 54% lower than in the control group (P < 0.05). Fluorescence intensity was positively correlated with the nodule area (R 2 = 0.8859; P < 0.001) and MVA (R 2 = 0.9431; P < 0.001) in the ES-treated group. These results demonstrate that the spectroscopic analysis method allows a selective detection of tumor masses. This preliminary study suggests that PpIX fluorescence may be useful as a biomarker for antiangiogenic cancer therapy.

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

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

Similar content being viewed by others

References

  1. Tonini T, Rossi F, Claudio PP (2003) Molecular basis of angiogenesis and cancer. Oncogene 22:6549–6556

    Article  CAS  PubMed  Google Scholar 

  2. Gupta K, Miller JD, Li JZ, Russell MW, Charbonneau C (2008) Epidemiologic and socioeconomic burden of metastatic renal cell carcinoma (mRCC): a literature review. Cancer Treat Rev 34:193–205

    Article  PubMed  Google Scholar 

  3. Chow WH, Devesa SS, Warren JL, Fraumeni JF Jr (1999) Rising incidence of renal cell cancer in the United States. JAMA 281:1628–1631

    Article  CAS  PubMed  Google Scholar 

  4. Hollingsworth JM, Miller DC, Daignault S, Hollenbeck BK (2007) Five-year survival after surgical treatment for kidney cancer: a population–based competing risk analysis. Cancer 109:1763–1768

    Article  PubMed  Google Scholar 

  5. Assouad J, Petcova B, Berna P, Dujon A, Foucault C, Riquet M (2007) Renal cell carcinoma metastases surgery: pathologic findings and prognostic factors. Ann Thorac Surg 84(4):1114–1120

    Article  PubMed  Google Scholar 

  6. Weiss L, Harlos JP, Torhost J, Gunthard B, Hartveit F, Svendsen E, Huang WL, Grundmann E, Eder M, Zwicknagl M, Cochrane HR, Stock D, Wright C, Horne CHW (1988) Metastatic patterns of renal carcinoma: an analysis of 687 necropsies. J Cancer Res Clin Oncol 114:605–612

    Article  CAS  PubMed  Google Scholar 

  7. Saitoh H (1981) Distant metastasis of renal adenocarcinoma. Cancer 48:1487–1491

    Article  CAS  PubMed  Google Scholar 

  8. Coutinho EL, Andrade LNS, Chammas R, Morganti L, Schor N, Bellini MH (2007) Anti-tumor effect of endostatin mediated by retroviral gene transfer in mice bearing renal cell carcinoma. FASEB J 21:3153–3161

    Article  CAS  PubMed  Google Scholar 

  9. Kerbel R, Folkman J (2002) Clinical translation of angiogenesis inhibitors. Nat Rev Cancer 2:727–739

    Article  CAS  PubMed  Google Scholar 

  10. Martin-Padura I, Bertolini F (2009) Circulating endothelial cells as biomarkers for angiogenesis in tumor progression. Front Biosci (Schol Ed) 1:304–318

    Google Scholar 

  11. Folkman J (2004) Endogenous angiogenesis inhibitors. APMIS 112:496–507

    Article  CAS  PubMed  Google Scholar 

  12. Boehm T, Folkman J, Browder T, O’Relly MS (1997) Antiangiogenic therapy of experimental cancer does not induce acquired drug resistance. Nature 390:404–407

    Article  CAS  PubMed  Google Scholar 

  13. O’Reilly MS, Boehm T, Shing Y, Fukai N, Vasios G, Lane WS, Flynn E, Birkhead JR, Olsen BR, Folkman J (1997) Endostatin: an endogenous inhibitor of angiogenesis and tumor growth. Cell 88:277–285

    Article  PubMed  Google Scholar 

  14. Kirsch M, Schackert G, Black PM (2000) Angiogenesis, metastasis, and endogenous inhibition. J Neuro-oncology 50:173–180

    Article  CAS  Google Scholar 

  15. Te Velde EA, Vogten JM, Gebbink MFGB, Van Gorp JM, Voest EE, Rinkes IHMB (2002) Enhanced antitumour efficacy by combining conventional chemotherapy with angiostatin or endostatin in a liver metastasis model. Br J Surg 89:1302–1309

    Article  CAS  PubMed  Google Scholar 

  16. Schantz SP, Savage HE, Sacks P, Alfano RR (1997) Native cellular fluorescence and its application to cancer prevention. Environ Health Perspect 105(Suppl 4):941

    Article  CAS  PubMed  Google Scholar 

  17. Ramanujam N (2000) Fluorescence spectroscopy of neoplastic and non-neoplastic tissues. Neoplasia 2(1–2):89–117

    Article  CAS  PubMed  Google Scholar 

  18. Chang KS, Ina P, Marin N, Follen M, Richards-Kortum R (2005) Fluorescence spectroscopy as a diagnostic tool for detecting cervical pre-cancer. Gynecol Oncol 99:S61–S63

    Article  PubMed  Google Scholar 

  19. Vogeser M, Jacob K, Zachoval R (2000) Erythrocyte protoporphyrins in hepatitis C viral infection. Clin Biochem 33(5):387–391

    Article  CAS  PubMed  Google Scholar 

  20. Courrol LC, Silva FRO, Coutinho EL, Piccoli MF, Mansano RD, Vieira ND, Schor N, Bellini MH (2007) Study of blood porphyrin spectral profile for diagnosis of tumor progression. J Fluoresc 17(3):289–292

    Article  CAS  PubMed  Google Scholar 

  21. Bellini MH, Coutinho EL, Courrol LC, Silva FRO, Vieira ND, Schor N (2008) Correlation between autofluorescence intensity and tumor area in mice bearing renal cell carcinoma. J Fluoresc 18(6):1163–1168

    Article  CAS  PubMed  Google Scholar 

  22. Kusunoki Y, Imamura F, Uda H, Mano M, Horai T (2000) Early detection of lung cancer with laser-induced fluorescence endoscopy and spectrofluorometry. Chest 118:1776–1782

    Article  CAS  PubMed  Google Scholar 

  23. Tsai TM, Hong RL, Tsai JC (2004) Effect of 5-aminolevulinic acid-mediated photodynamic therapy on MCF-7 and MCF-7/ADR cells. Lasers Surg Med 34:64–72

    Google Scholar 

  24. Heyerdahl H, Wang I, Liu DL, Berg R, Andersson-Engels S, Peng Q, Moan J, Svanberg S, Svanberg K (1997) Pharmacokinetic studies on 5-aminolevulinic acid-induced protoporphyrin IX, accumulation in tumors and normal tissues. Cancer Lett 112:225–231

    Article  CAS  PubMed  Google Scholar 

  25. Malik Z, Kostenich G, Roitman L, Ehrenberg B, Orenstein A (1995) Topical application of 5-aminolevulinic acid, DMSO and EDTA: protoporphyrin IX accumulation in skin and tumors of mice. J Photochem Photobiol B 28:213–218

    Article  CAS  PubMed  Google Scholar 

  26. Van Der Breggen EWJ, Rem AI, Cristian MM, Yang CJ, Calhoun KH, Sterenborg HJCM, Motamedi M (1996) Spectroscopic detection of oral and skin tissue transformation in a model for squamous cell carcinoma: autofluorescence versus systemic aminolevulinic acid-induced fluorescence. IEEE J Sel Top Quantum Electron 2:997–1007

    Article  Google Scholar 

  27. Moesta KT, Ebert B, Handke T, Nolte D, Nowak C, Haensch WE, Pandey RK, Dougherty TJ, Rinneberg H, Schlag PM (2001) Protoporphyrin IX occurs naturally in colorectal cancers and their metastases. Cancer Res 61:991–999

    CAS  PubMed  Google Scholar 

  28. Tsuji T, Sasaki Y, Tanaka M, Hanabata N, Hada R, Munakata A (2002) Microvessel morphology and vascular endothelial growth factor expression in human colonic carcinoma with or without metastasis. Lab Invest 82:555–562

    Article  CAS  PubMed  Google Scholar 

  29. Hlatky L, Hahnfeldt P, Folkman J (2002) Clinical application of antiangiogenic therapy: microvessel density, what it does and doesn’t tell us. J Natl Cancer Inst 94:883–893

    PubMed  Google Scholar 

Download references

Acknowledgements

This study was supported by FAPESP [Process number: 07/54253-6] and CNPq [Process number: 481888/2008].

Author information

Authors and Affiliations

  1. Centro de Biotecnologia, IPEN/CNEN-SP, São Paulo, SP, Brazil

    Flávia Gomes de Góes Rocha, Karen Cristina Barbosa Chaves, Cinthia Zanini Gomes & Maria Helena Bellini

  2. Disciplina de Nefrologia, Departamento de Medicina, UNIFESP, São Paulo, SP, Brazil

    Flávia Gomes de Góes Rocha, Karen Cristina Barbosa Chaves, Camila Barricheli Campanharo, Nestor Schor & Maria Helena Bellini

  3. Departamento de Ciências Exatas e da Terra, UNIFESP, São Paulo, SP, Brazil

    Lilia Coronato Courrol

  4. Centro de Lasers e Aplicações, IPEN/CNEN-SP, São Paulo, SP, Brazil

    Lilia Coronato Courrol

Authors
  1. Flávia Gomes de Góes Rocha
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Karen Cristina Barbosa Chaves
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. Cinthia Zanini Gomes
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Camila Barricheli Campanharo
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Lilia Coronato Courrol
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Nestor Schor
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. Maria Helena Bellini
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Maria Helena Bellini.

Rights and permissions

Reprints and permissions

About this article

Cite this article

de Góes Rocha, F.G., Chaves, K.C.B., Gomes, C.Z. et al. Erythrocyte Protoporphyrin Fluorescence as a Biomarker for Monitoring Antiangiogenic Cancer Therapy. J Fluoresc 20, 1225–1231 (2010). https://doi.org/10.1007/s10895-010-0672-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10895-010-0672-7

Keywords

Search

Navigation