A proteomic analysis of the effect of radiation therapy on wound healing in women reconstructed with the TRAM flap

Abstract

The incidence of breast cancer is still increasing, and with improved cancer treatment, more women live longer with the side effects of their treatment. The response of normal tissue to radiation continues for years after the treatment is completed. The influence of radiotherapy on the outcome of breast reconstructtive surgery remains unpredictable. The combination of two surgical sites of which one is previously irradiated, is rarely encountered in humans and thus compiles a unique opportunity to study the implications of irradiation followed by surgery. The aim of this study was to examine the long-term effect of radiation therapy on the proteins expressed in the wound tissue after a breast reconstruction. Ten patients were included in the study, all treated with radiotherapy after a mastectomy and breast reconstruction with a contralateral pedicled TRAM flap. Expanded poly-tetrafluoretylene polymer tubes were implanted for 10 days, subcutaneously, below the inframammary fold and below the donor site. The protein from the newly synthesized granulation tissue in the tubes was extracted and analyzed for differences in protein expression with 2D gel electrophoresis and mass spectrometry. A total of 676 proteins were detected; of these, 4 proteins changed significantly and were successfully identified. TPM4 and APOA4 from the radiation treated tissue were shown to be significantly decreased, whereas IGKC and VDAC1 were found to be significantly increased. The proteomic technique combined with the ePTFE tube wound model can elucidate some of the molecular alterations in the wound healing induced by radiation therapy. The protein modifications of TPM4, APOA4, IGKC and VDAC1 may influence the cell proliferation, apoptosis and the inflammation of the tissue repair process. 

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Christensen, B. , Overgaard, J. , Vorum, H. , Honore, B. and Damsgaard, T. (2013) A proteomic analysis of the effect of radiation therapy on wound healing in women reconstructed with the TRAM flap. Advances in Bioscience and Biotechnology, 4, 1007-1012. doi: 10.4236/abb.2013.411134.

Conflicts of Interest

The authors declare no conflicts of interest.

References

[1] [1] Dormand, E.L., Banwell, P.E. and Goodacre, T.E. (2005) Radiotherapy and wound healing. International Wound Journal, 2, 112-127.
http://dx.doi.org/10.1111/j.1742-4801.2005.00079.x
[2] Christensen, B., Overgaard, J., Kettner, L.O. and Damsgaard, T.E. (2013) Long-term evaluation of postmastectomy breast reconstruction with the TRAM flap. Journal of Plastic Surgery and Hand Surgery.
[3] Bristol, S.G., Lennox, P.A. and Clugston, P.A. (2006) A comparison of ipsilateral pedicled TRAM flap with and without previous irradiation. Annals of Plastic Surgery, 56, 589-592.
http://dx.doi.org/10.1097/01.sap.0000205057.23543.48
[4] Spear, S.L., Ducic, I., Low, M. and Cuoco F. (2005) The effect of radiation on pedicled TRAM flap breast reconstruction: Outcomes and implications. Plastic and Reconstractive Surgery, 115, 84-95.
[5] Carlson, G.W., Page, A.L., Peters, K., Ashinoff, R., Schaefer, T. and Losken, A. (2008) Effects of radiation therapy on pedicled transverse rectus abdominis myocutaneous flap breast reconstruction. Annals of Plastic Surgery May, 60, 568-572.
http://dx.doi.org/10.1097/SAP.0b013e31815b6ced
[6] Williams, J.K., Bostwick, J. III, Bried, J.T., Mackay, G., Landry, J. and Benton, J. (1995) TRAM flap breast reconstruction after radiation treatment. Annals of Surgery, 221, 756-764.
http://dx.doi.org/10.1097/00000658-199506000-00014
[7] Denham, J.W. and Hauer-Jensen, M. (2002) The radiotherapeutic injury—A complex “wound”. Radiotherapy & Oncology, 63, 129-145.
http://dx.doi.org/10.1016/S0167-8140(02)00060-9
[8] Devalia, H.L. and Mansfield, L. (2008) Radiotherapy and wound healing. International Wound Journal, 5, 40-44.
http://dx.doi.org/10.1111/j.1742-481X.2007.00351.x
[9] Johnson L.B., Adawi D., Agren M.S., Jorgensen L.N., Wittgren L., Mattsson S., et al. (2006) Combination of pre-operative radiotherapy and surgery suppresses local accumulation of collagen and TGF-β1 in rats. Journal of Surgical Research, 133, 136-142.
http://dx.doi.org/10.1016/j.jss.2005.12.012
[10] Blumenberg, M. (2005) Skinomics. Journal of Investigative Dermatology, 124, viii-viix.
http://dx.doi.org/10.1111/j.0022-202X.2004.23639.x
[11] Menard, C., Johann, D., Lowenthal, M., Muanza, T., Sproull, M., Ross, S., et al. (2006) Discovering clinical biomarkers of ionizing radiation exposure with serum proteomic analysis. Cancer Research, 66, 1844-1850.
http://dx.doi.org/10.1158/0008-5472.CAN-05-3466
[12] Bernstein, E.F., Harisiadis, L., Salomon, G., Norton, J., Sollberg, S., Uitto, J., et al. (1991) Transforming growth factor-β improves healing of radiation-impaired wounds. Journal of Investigative Dermatology, 97, 430-434.
http://dx.doi.org/10.1111/1523-1747.ep12481258
[13] Schultze-Mosgau, S., Wehrhan, F., Amann, K., Radespiel-Troger, M., Rodel, F. and Grabenbauer, G.G. (2003) In Vivo TGF-β3 expression during wound healing in irradiated tissue. An experimental study. Strahlentherapie und Onkologie, 179, 410-416.
[14] Jorgensen, L.N. (2003) Collagen deposition in the subcutaneous tissue during wound healing in humans: A model evaluation. APMIS. Supplementum, 115, 1-56.
[15] Overgaard, M. and Christensen, J.J. (2008) Postoperative radiotherapy in DBCG during 30 years. Techniques, indications and clinical radiobiological experience. Acta Oncologica, 47, 639-653.
http://dx.doi.org/10.1080/02841860802078085
[16] Mandal, N., Lewis, G.P., Fisher, S.K., Heegaard, S., Prause, J.U., la, C.M., et al. (2011) Protein changes in the retina following experimental retinal detachment in rabbits. Molecular Vision, 17, 2634-2648.
[17] Backovic, A., Huang, H.L., Del, F.B., Piza, H., Huber, L.A. and Wick, G. (2007) Identification and dynamics of proteins adhering to the surface of medical silicones in vivo and in vitro. Journal of Proteome Research, 6, 376-381.
http://dx.doi.org/10.1021/pr0603755
[18] Li, D.Q., Wang, L., Fei, F., Hou, Y.F., Luo, J.M., Zeng, R., et al. (2006) Identification of breast cancer metastasis-associated proteins in an isogenic tumor metastasis model using two-dimensional gel electrophoresis and liquid chromatography-ion trap-mass spectrometry. Proteomics, 6, 3352-3368. http://dx.doi.org/10.1002/pmic.200500617
[19] Shoshan-Barmatz, V., Keinan, N. and Zaid, H. (2008) Uncovering the role of VDAC in the regulation of cell life and death. Journal of Bioenergetics and Biomembranes, 40, 183-191. http://dx.doi.org/10.1007/s10863-008-9147-9
[20] Voehringer, D.W., Hirschberg, D.L., Xiao, J., Lu, Q., Roederer, M., Lock, C.B., et al. (2000) Gene microarray identification of redox and mitochondrial elements that control resistance or sensitivity to apoptosis. Proceedings of the National Academy of Science of the United States of America, Vol. 97, No. 6, 2000, pp. 2680-2685.
http://dx.doi.org/10.1073/pnas.97.6.2680
[21] Ebrini, I., Agnello, D., Miller, I., Villa, P., Fratelli, M., Ghezzi, P., et al. (2000) Proteins of rat serum V: Adjuvant arthritis and its modulation by nonsteroidal anti-inflammatory drugs. Electrophoresis, 21, 2170-2179.
http://dx.doi.org/10.1002/1522-2683(20000601)21:11<2170::AID-ELPS2170>3.0.CO;2-1

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