Analytical and Bioanalytical Chemistry

, Volume 387, Issue 5, pp 1621–1631

Biomolecular profiling of metastatic prostate cancer cells in bone marrow tissue using FTIR microspectroscopy: a pilot study

  • E. Gazi
  • J. Dwyer
  • N. P. Lockyer
  • P. Gardner
  • J. H. Shanks
  • J. Roulson
  • C. A. Hart
  • N. W. Clarke
  • M. D. Brown
Original Paper

Abstract

Prostate cancer (CaP) cells preferentially metastasise to the bone marrow, a microenvironment that plays a substantial role in the sustenance and progression of the CaP tumour. Here we use a combination of FTIR microspectroscopy and histological stains to increase molecular specificity and probe the biochemistry of metastatic CaP cells in bone marrow tissue derived from a limited source of paraffin-embedded biopsies of different patients. This provides distinction between the following dominant metabolic processes driving the proliferation of the metastatic cells in each of these biopsies: glycerophospholipid synthesis from triacylglyceride, available from surrounding adipocytes, in specimen 1, through significantly high (p ≤ 0.05) carbohydrate (8.23 ± 1.44 cm−1), phosphate (6.13 ± 1.5 cm−1) and lipid hydrocarbon (24.14 ± 5.9 cm−1) signals compared with the organ-confined CaP control (OC CaP), together with vacuolation of cell cytoplasm; glycolipid synthesis in specimen 2, through significantly high (p ≤ 0.05) carbohydrate (5.51 ± 0.04 cm−1) and high lipid hydrocarbon (17.91 ± 2.3 cm−1) compared with OC CaP, together with positive diastase-digested periodic acid Schiff staining in the majority of metastatic CaP cells; glycolysis in specimen 3, though significantly high (p ≤ 0.05) carbohydrate (8.86 ± 1.78 cm−1) and significantly lower (p ≤ 0.05) lipid hydrocarbon (11.67 ± 0.4 cm−1) than OC CaP, together with negative diastase-digested periodic acid Schiff staining in the majority of metastatic CaP cells. Detailed understanding of the biochemistry underpinning the proliferation of tumour cells at metastatic sites may help towards refining chemotherapeutic treatment.

Keywords

Prostate cancer Infrared microspectroscopy Metastases Lipid 

References

  1. 1.
    Cancer Research UK (2002) Cancer stats, incidence UK. June 2002, Cancer Research UK. http://www.cancerresearchuk.org/images/11632/cancerstats_incidence_2002.pdf accessed 10 April 2006
  2. 2.
    Cancer Research UK (2002) Cancer stats, mortality UK. June 2002, Cancer Research UK. http://www.cancerresearchuk.org/images/11632/cancerstats_mortality2003.pdf accessed 10 April 2006
  3. 3.
    Salazar OM, Rubin P, Hendrickson FR (1986) Cancer 58:29–36CrossRefGoogle Scholar
  4. 4.
    George NJ (1988) Lancet 1:494–497CrossRefGoogle Scholar
  5. 5.
    Compston JE (2002) J Endocrinol 172:387–394CrossRefGoogle Scholar
  6. 6.
    Hauschuka PV, Manrakos AE, Iafrati MD, Doleman SE, Klagsbrun M (1986) J Biol Chem 261:12665–12674Google Scholar
  7. 7.
    N∅rgaard P, Hougaard S, Poulsen HS, Spang-Thomsen M (1995) Cancer Treat Rev 21:367–403CrossRefGoogle Scholar
  8. 8.
    Clarke NW, McClure J, George NJ (1991) Brit J Cancer 68:74–80Google Scholar
  9. 9.
    Heidenreich A (2003) Oncology 65(Suppl):5–11CrossRefGoogle Scholar
  10. 10.
    The nations investment in cancer research. A plan and budget proposal for fiscal year 2005. http://cancer.gov/pdf/nci_2005_plan.p.16-21
  11. 11.
    Sahu RK, Argov S, Bernshtain E, Salman A, Walfisch S, Goldstein J, Mordechai S (2004) Scand J Gastroenterol 6:558–566Google Scholar
  12. 12.
    Gazi E, Dwyer J, Gardner P, Ghanbari-Siahkali A, Wade A, Miyan J, Lockyer NP, Vickerman JC, Clarke NW, Shanks JH, Scott LJ, Hart C, Brown M (2003) J Path 201:99–108CrossRefGoogle Scholar
  13. 13.
    Brown MD, Hart CA, Gazi E, Bagley S, Clarke NW (2006) Brit J Cancer 94:842–853CrossRefGoogle Scholar
  14. 14.
    Giovannucci E, Rimm EB, Colditz GA, Stampfer MJ, Ascherio A, Chute CC, Willett WC (1994) J Nat Cancer Inst 86:1571–1579CrossRefGoogle Scholar
  15. 15.
    Mamalakis G, Kafatos A, Kalogeropoulos N, Andrikopoulos N, Daskalopulos G, Kranidis A (2002) Prostaglandins, Leukot Essent Fat Acids 66(5–6):467–477CrossRefGoogle Scholar
  16. 16.
    Tokuda Y, Satoh Y, Fujiyama C, Sugihara H, Masaki Z (2003) Brit J Urol Int 91:716–720Google Scholar
  17. 17.
    Parton RG, Simona K (1995) Science 269:1398–1399CrossRefGoogle Scholar
  18. 18.
    Gazi E, Dwyer J, Lockyer NP, Gardner P, Miyan J, Hart CA, Brown MD, Clarke NW (2005) Biopolymers 77:18–30CrossRefGoogle Scholar
  19. 19.
    Chalmers JM, Griffiths PR (eds) (2002) Handbook of vibrational spectroscopy, vol 5. Wiley, ItalyGoogle Scholar
  20. 20.
    Chalmers JM, Griffiths PR (eds) (2002) Handbook of vibrational spectroscopy, vol 3. Wiley, ItalyGoogle Scholar
  21. 21.
    Petibois C, Gionnet K, Goncalves M, Perromat A, Moenner M, Deleris G (2006) Analyst 131:640–647CrossRefGoogle Scholar
  22. 22.
    Kieran JA (ed) (1990) Histological and histochemical methods: theory & practice. Pergamon, UKGoogle Scholar
  23. 23.
    Gomez-Fernandez JC, Villalain J (1998) Chem Phys Lipids 96:41–52CrossRefGoogle Scholar
  24. 24.
    Pizer ES, Chrest FJ, DiGiuseppe JA, Han WF (1998) Cancer Res 58:4611–4615Google Scholar
  25. 25.
    Lewis CE, Pusztai L, Yap E (eds) (1996) Cell proliferation in cancer: regulatory mechanisms of neoplastic cell growth. Oxford University Press, New YorkGoogle Scholar

Copyright information

© Springer-Verlag 2007

Authors and Affiliations

  • E. Gazi
    • 1
    • 3
  • J. Dwyer
    • 1
  • N. P. Lockyer
    • 1
  • P. Gardner
    • 1
  • J. H. Shanks
    • 2
  • J. Roulson
    • 2
    • 3
  • C. A. Hart
    • 3
  • N. W. Clarke
    • 3
    • 4
  • M. D. Brown
    • 3
  1. 1.School of Chemical Engineering and Analytical ScienceThe University of ManchesterManchesterUK
  2. 2.Histopathology DepartmentChristie Hospital NHS TrustManchesterUK
  3. 3.ProMPT Genito Urinary Cancer Research Group, The Paterson Institute for Cancer ResearchThe University of Manchester, Christie Hospital NHS TrustManchesterUK
  4. 4.Department of UrologyHope Hospital NHS TrustManchesterUK
  5. 5.ProMPT Genito-Urinary Cancer Research, Cancer Research UK Paterson InstituteChristie Hospital NHS TrustManchesterUK

Personalised recommendations