Skip to main content
British Journal of Cancer logoLink to British Journal of Cancer
. 1999 Jul;80(10):1512–1517. doi: 10.1038/sj.bjc.6690554

Induction of Fos protein expression in spinal cord neurons of tumour-bearing rats

S Kergozien 1, J-G Delcros 1, H Jouan 1, J-P Moulinoux 1
PMCID: PMC2363164  PMID: 10408391

Abstract

The absence of discernible abnormal symptoms such as pain, often leading to delayed diagnosis in cancer patients, may be indicative of a dysregulation in sensory transmission between the tumour and the central nervous system. We explored expression of Fos protein in spinal cord neurons in rats, during the development of the MAT-LyLu prostatic adenocarcinoma grafted on the hind limb. The tumour triggered the densest Fos labelling in the L3–L5 lumbar segments, ipsilateral to the grafted limb. The labelling, detected at day 5, increased until day 10 and dropped off thereafter. The ventral horn (except lamina IX) was the most densely labelled region. Histological examination of the grafted limbs demonstrated that no inflammatory reaction accompanied the tumour growth. Rats exhibited no behavioural alterations either spontaneous or induced by handling. These results demonstrate that signals are sent to the central nervous system by the peripheral tumour. Considering both the behavioural and histological observations, it is unlikely that spinal activity reflects a painful state. The nature of these signals, inefficient to trigger the appropriate reaction of the organism against the tumour, remain to be determined with regard to the pharmacologically active compounds synthesized and released by the tumour cells. © 1999 Cancer Research Campaign

Keywords: prostatic carcinoma, Fos, spinal cord, rat, pain

Full Text

The Full Text of this article is available as a PDF (152.6 KB).

Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Abbadie C., Besson J. M. c-fos expression in rat lumbar spinal cord during the development of adjuvant-induced arthritis. Neuroscience. 1992 Jun;48(4):985–993. doi: 10.1016/0306-4522(92)90287-c. [DOI] [PubMed] [Google Scholar]
  2. Bennett G. J., Abdelmoumene M., Hayashi H., Dubner R. Physiology and morphology of substantia gelatinosa neurons intracellularly stained with horseradish peroxidase. J Comp Neurol. 1980 Dec 15;194(4):809–827. doi: 10.1002/cne.901940407. [DOI] [PubMed] [Google Scholar]
  3. Besson J. M., Chaouch A. Peripheral and spinal mechanisms of nociception. Physiol Rev. 1987 Jan;67(1):67–186. doi: 10.1152/physrev.1987.67.1.67. [DOI] [PubMed] [Google Scholar]
  4. Carlton S. M., Hargett G. L., Coggeshall R. E. Localization and activation of glutamate receptors in unmyelinated axons of rat glabrous skin. Neurosci Lett. 1995 Sep 1;197(1):25–28. doi: 10.1016/0304-3940(95)11889-5. [DOI] [PubMed] [Google Scholar]
  5. Chi S. I., Levine J. D., Basbaum A. I. Peripheral and central contributions to the persistent expression of spinal cord fos-like immunoreactivity produced by sciatic nerve transection in the rat. Brain Res. 1993 Jul 23;617(2):225–237. doi: 10.1016/0006-8993(93)91090-f. [DOI] [PubMed] [Google Scholar]
  6. Harris J. A. Using c-fos as a neural marker of pain. Brain Res Bull. 1998;45(1):1–8. doi: 10.1016/s0361-9230(97)00277-3. [DOI] [PubMed] [Google Scholar]
  7. Hsu S. M., Raine L., Fanger H. A comparative study of the peroxidase-antiperoxidase method and an avidin-biotin complex method for studying polypeptide hormones with radioimmunoassay antibodies. Am J Clin Pathol. 1981 May;75(5):734–738. doi: 10.1093/ajcp/75.5.734. [DOI] [PubMed] [Google Scholar]
  8. Hughes P., Dragunow M. Induction of immediate-early genes and the control of neurotransmitter-regulated gene expression within the nervous system. Pharmacol Rev. 1995 Mar;47(1):133–178. [PubMed] [Google Scholar]
  9. Hunt S. P., Pini A., Evan G. Induction of c-fos-like protein in spinal cord neurons following sensory stimulation. Nature. 1987 Aug 13;328(6131):632–634. doi: 10.1038/328632a0. [DOI] [PubMed] [Google Scholar]
  10. Isaacs J. T., Yu G. W., Coffey D. S. The characterization of a newly identified, highly metastatic variety of Dunning R 3327 rat prostatic adenocarcinoma system: the MAT LyLu tumor. Invest Urol. 1981 Jul;19(1):20–23. [PubMed] [Google Scholar]
  11. Jänne J., Pösö H., Raina A. Polyamines in rapid growth and cancer. Biochim Biophys Acta. 1978 Apr 6;473(3-4):241–293. doi: 10.1016/0304-419x(78)90015-x. [DOI] [PubMed] [Google Scholar]
  12. Lantéri-Minet M., de Pommery J., Herdegen T., Weil-Fugazza J., Bravo R., Menétrey D. Differential time course and spatial expression of Fos, Jun, and Krox-24 proteins in spinal cord of rats undergoing subacute or chronic somatic inflammation. J Comp Neurol. 1993 Jul 8;333(2):223–235. doi: 10.1002/cne.903330208. [DOI] [PubMed] [Google Scholar]
  13. Martin H. A., Basbaum A. I., Kwiat G. C., Goetzl E. J., Levine J. D. Leukotriene and prostaglandin sensitization of cutaneous high-threshold C- and A-delta mechanonociceptors in the hairy skin of rat hindlimbs. Neuroscience. 1987 Aug;22(2):651–659. doi: 10.1016/0306-4522(87)90360-5. [DOI] [PubMed] [Google Scholar]
  14. Marton L. J., Pegg A. E. Polyamines as targets for therapeutic intervention. Annu Rev Pharmacol Toxicol. 1995;35:55–91. doi: 10.1146/annurev.pa.35.040195.000415. [DOI] [PubMed] [Google Scholar]
  15. Molander C., Hongpaisan J., Grant G. Changing pattern of c-FOS expression in spinal cord neurons after electrical stimulation of the chronically injured sciatic nerve in the rat. Neuroscience. 1992 Sep;50(1):223–236. doi: 10.1016/0306-4522(92)90394-h. [DOI] [PubMed] [Google Scholar]
  16. Molander C., Xu Q., Grant G. The cytoarchitectonic organization of the spinal cord in the rat. I. The lower thoracic and lumbosacral cord. J Comp Neurol. 1984 Nov 20;230(1):133–141. doi: 10.1002/cne.902300112. [DOI] [PubMed] [Google Scholar]
  17. Morgan J. I., Cohen D. R., Hempstead J. L., Curran T. Mapping patterns of c-fos expression in the central nervous system after seizure. Science. 1987 Jul 10;237(4811):192–197. doi: 10.1126/science.3037702. [DOI] [PubMed] [Google Scholar]
  18. Morgan J. I., Curran T. Role of ion flux in the control of c-fos expression. Nature. 1986 Aug 7;322(6079):552–555. doi: 10.1038/322552a0. [DOI] [PubMed] [Google Scholar]
  19. Morgan J. I., Curran T. Stimulus-transcription coupling in the nervous system: involvement of the inducible proto-oncogenes fos and jun. Annu Rev Neurosci. 1991;14:421–451. doi: 10.1146/annurev.ne.14.030191.002225. [DOI] [PubMed] [Google Scholar]
  20. Moulinoux J. P., Quemener V., Larzul J. J., Le Calve M., Roch A. M., Toujas L., Quash G. Red blood cell polyamines in mice bearing the Lewis lung carcinoma (3LL) and in patients with bronchopulmonary cancers. Int J Cancer. 1984 Aug 15;34(2):277–281. doi: 10.1002/ijc.2910340221. [DOI] [PubMed] [Google Scholar]
  21. Munglani R., Hunt S. P. Proto-oncogenes: basic concepts and stimulation induced changes in the spinal cord. Prog Brain Res. 1995;104:283–298. doi: 10.1016/s0079-6123(08)61796-3. [DOI] [PubMed] [Google Scholar]
  22. Müller R., Bravo R., Burckhardt J., Curran T. Induction of c-fos gene and protein by growth factors precedes activation of c-myc. Nature. 1984 Dec 20;312(5996):716–720. doi: 10.1038/312716a0. [DOI] [PubMed] [Google Scholar]
  23. Presley R. W., Menétrey D., Levine J. D., Basbaum A. I. Systemic morphine suppresses noxious stimulus-evoked Fos protein-like immunoreactivity in the rat spinal cord. J Neurosci. 1990 Jan;10(1):323–335. doi: 10.1523/JNEUROSCI.10-01-00323.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Shaw M. W., Ablin R. J., Ray P., Rubenstein M., Guinan P. D., McKiel C. F. Immunobiology of the Dunning R-3327 rat prostate adenocarcinoma sublines: plasma and tumor effusion prostaglandins. Am J Reprod Immunol Microbiol. 1985 Jul;8(3):77–79. doi: 10.1111/j.1600-0897.1985.tb00312.x. [DOI] [PubMed] [Google Scholar]
  25. Swett J. E., Woolf C. J. The somatotopic organization of primary afferent terminals in the superficial laminae of the dorsal horn of the rat spinal cord. J Comp Neurol. 1985 Jan 1;231(1):66–77. doi: 10.1002/cne.902310106. [DOI] [PubMed] [Google Scholar]
  26. Williams K. Interactions of polyamines with ion channels. Biochem J. 1997 Jul 15;325(Pt 2):289–297. doi: 10.1042/bj3250289. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Zhang M., Caragine T., Wang H., Cohen P. S., Botchkina G., Soda K., Bianchi M., Ulrich P., Cerami A., Sherry B. Spermine inhibits proinflammatory cytokine synthesis in human mononuclear cells: a counterregulatory mechanism that restrains the immune response. J Exp Med. 1997 May 19;185(10):1759–1768. doi: 10.1084/jem.185.10.1759. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Zhou S., Bonasera L., Carlton S. M. Peripheral administration of NMDA, AMPA or KA results in pain behaviors in rats. Neuroreport. 1996 Mar 22;7(4):895–900. doi: 10.1097/00001756-199603220-00012. [DOI] [PubMed] [Google Scholar]

Articles from British Journal of Cancer are provided here courtesy of Cancer Research UK

RESOURCES