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. 2000 Aug 16;83(5):650–654. doi: 10.1054/bjoc.2000.1321

Increased collagen production in fibroblasts cultured from irradiated skin and effect of TGF β1– clinical study

M C Illsley 1, J H Peacock 1, R J McAnulty 2, J R Yarnold 3
PMCID: PMC2363497  PMID: 10944607

Abstract

Fibrosis in normal tissues is a common and dose-limiting late complication of radiotherapy at many cancer sites, but its pathogenesis is poorly understood. We undertook a controlled study of the effect of irradiation on the collagen production of fibroblasts cultured from skin biopsies taken from patients undergoing radiotherapy treatment. Eight weeks after a single 8 Gy fraction using 300 kV X-rays, five patients treated at the Royal Marsden Hospital underwent biopsy of the irradiated site and of the contralateral, unirradiated body site. Fibroblasts from irradiated and control, unirradiated sites were cultured in vitro, and collagen production rates were measured during a 48-hour incubation under standardized conditions and in the presence and absence of transforming growth factor β1(TGF β1), 1 ng/ml, using HPLC. Collagen production was elevated in cells cultured from irradiated skin; median collagen production rates 61.16 pmoles hydroxyproline/105cells/hour in irradiated cells, 39.78 pmoles hydroxyproline/105cells/hour in unirradiated cells, P = 0.016 (Mann–Whitney U-test). In fibroblasts from unirradiated sites, collagen production rates were increased by the addition of TGF β1; however, in three of the cell lines cultured from irradiated sites this effect of TGF β1 on collagen production was not observed. © 2000 Cancer Research Campaign

Keywords: radiotherapy, fibroblasts, radiation fibrosis, collagen, transforming growth factor beta

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Selected References

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  1. Autio P., Saarto T., Tenhunen M., Elomaa I., Risteli J., Lahtinen T. Demonstration of increased collagen synthesis in irradiated human skin in vivo. Br J Cancer. 1998 Jun;77(12):2331–2335. doi: 10.1038/bjc.1998.387. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Barcellos-Hoff M. H. Radiation-induced transforming growth factor beta and subsequent extracellular matrix reorganization in murine mammary gland. Cancer Res. 1993 Sep 1;53(17):3880–3886. [PubMed] [Google Scholar]
  3. Campa J. S., McAnulty R. J., Laurent G. J. Application of high-pressure liquid chromatography to studies of collagen production by isolated cells in culture. Anal Biochem. 1990 May 1;186(2):257–263. doi: 10.1016/0003-2697(90)90076-l. [DOI] [PubMed] [Google Scholar]
  4. Canney P. A., Dean S. Transforming growth factor beta: a promotor of late connective tissue injury following radiotherapy? Br J Radiol. 1990 Aug;63(752):620–623. doi: 10.1259/0007-1285-63-752-620. [DOI] [PubMed] [Google Scholar]
  5. Finkelstein J. N., Johnston C. J., Baggs R., Rubin P. Early alterations in extracellular matrix and transforming growth factor beta gene expression in mouse lung indicative of late radiation fibrosis. Int J Radiat Oncol Biol Phys. 1994 Feb 1;28(3):621–631. doi: 10.1016/0360-3016(94)90187-2. [DOI] [PubMed] [Google Scholar]
  6. McAnulty R. J., Campa J. S., Cambrey A. D., Laurent G. J. The effect of transforming growth factor beta on rates of procollagen synthesis and degradation in vitro. Biochim Biophys Acta. 1991 Jan 31;1091(2):231–235. doi: 10.1016/0167-4889(91)90066-7. [DOI] [PubMed] [Google Scholar]
  7. McAnulty R. J., Chambers R. C., Laurent G. J. Regulation of fibroblast procollagen production. Transforming growth factor-beta 1 induces prostaglandin E2 but not procollagen synthesis via a pertussis toxin-sensitive G-protein. Biochem J. 1995 Apr 1;307(Pt 1):63–68. doi: 10.1042/bj3070063. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Moulin V., Auger F. A., O'Connor-McCourt M., Germain L. Fetal and postnatal sera differentially modulate human dermal fibroblast phenotypic and functional features in vitro. J Cell Physiol. 1997 Apr;171(1):1–10. doi: 10.1002/(SICI)1097-4652(199704)171:1<1::AID-JCP1>3.0.CO;2-S. [DOI] [PubMed] [Google Scholar]
  9. Randall K., Coggle J. E. Long-term expression of transforming growth factor TGF beta 1 in mouse skin after localized beta-irradiation. Int J Radiat Biol. 1996 Sep;70(3):351–360. doi: 10.1080/095530096145085. [DOI] [PubMed] [Google Scholar]
  10. Rodemann H. P., Bamberg M. Cellular basis of radiation-induced fibrosis. Radiother Oncol. 1995 May;35(2):83–90. doi: 10.1016/0167-8140(95)01540-w. [DOI] [PubMed] [Google Scholar]
  11. Rudolph R., Vande Berg J., Schneider J. A., Fisher J. C., Poolman W. L. Slowed growth of cultured fibroblasts from human radiation wounds. Plast Reconstr Surg. 1988 Oct;82(4):669–677. doi: 10.1097/00006534-198810000-00019. [DOI] [PubMed] [Google Scholar]
  12. Zhang D., Jacobberger J. W. TGF-beta 1 perturbation of the fibroblast cell cycle during exponential growth: switching between negative and positive regulation. Cell Prolif. 1996 Jun;29(6):289–307. doi: 10.1111/j.1365-2184.1996.tb01581.x. [DOI] [PubMed] [Google Scholar]
  13. el Nabout R., Martin M., Remy J., Kern P., Robert L., Lafuma C. Collagen synthesis and deposition in cultured fibroblasts from subcutaneous radiation-induced fibrosis. Modification as a function of cell aging. Matrix. 1989 Nov;9(5):411–420. doi: 10.1016/s0934-8832(89)80047-2. [DOI] [PubMed] [Google Scholar]

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