Abstract
Carcinogenesis and normal tissue regeneration share some common characteristics. In both states there is an active cellular proliferation and induction of the expression of potent mitogenic growth factors and receptors that promote the proliferative activity. Normal tissue regeneration is initiated by acute injury. Carcinogenesis is linked to prolonged chronic cellular injury by a variety of toxic agents including carcinogen. The major difference between the two processes is that in normal tissue repair, both cellular proliferation and growth factor expression are suppressed upon the healing of the wound. In contrast, in cancer and in some nonmalignant proliferative disorders cellular proliferation remains uncontrolled, and the expression of the mitogenic growth factors and receptors remains unsuppressed. It seems that in these disorders, the pathologic lesion is not the induction of growth factor and cytokine expression. Induction of these factors in response to acute or chronic injury appears to be a physiologic process aiming at the repair of the damage caused by the injury. What is abnormal in these pathologic states is a malfunction of the reversal mechanisms that normally control the suppression of the genes encoding for these growth factors and cytokines.
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References
H.N. Antoniades, Linking cellular injury to gene expression and human proliferative disorders: examples with the PDGF genes, Mol. Carcinog. 6: 175 (1992).
H.N. Antoniades, T. Galanopoulos, J. Neville-Golden, C.P. Kiritsy, and S.E. Lynch, Injury induces in vivo expression of PDGF and PDGF-receptor mRNAs in skin epithelial cells and PDGF mRNA in connective tissue fibroblasts, Proc. Natl. Acad. Sci. USA. 88: 565 (1991).
H.N. Antoniades, T. Galanopoulos, J. Neville-Golden, C.P. Kiritsy, and S.E. Lynch, Expression of growth factor and receptor mRNAs in skin epithelial cells following acute cutaneous injury, Am. J. Pathol. 142: 1099 (1993).
H.-A. Hansson, E. Jennische, and A. Skottner, Regenerating endothelial cell express insulin-like growth factor I immunoreactivity after arterial injury, Cell Tissue Res. 250: 499 (1987).
G.R. Grotendorst, C.A. Grotendorst, and T. Gilman, Production of growth factors (PDGF an TGF-beta) at the site of tissue repair, Prog. Clin. Biol. Res. 266: 47 (1988).
G.R. Grotendorst, Y. Soma, K. Takehara, and M. Charette, EGF and TGF-alpha are potent chemoattractants for endothelial cells and EGF-like peptides are present at sites of tissue regeneration. J. Cell Physiol. 139: 617 (1989).
H. Steefnos, C. Lossing, and H.A. Hansson, Immunohistochemical demonstration of endogenous growth factors in wound healing, Wounds 2: 218 (1990).
C.J.M. Kane, P.C. Hanawait, A.M. Knapp, and J.N. Mansbridge, Transforming growth factor-ßl localization normal and psoriatic epidermal keratinocytes in situ, J. Cell Physiol. 144: 144 (1990).
D.J. Whitby, and M.W. Ferguson, Immunohistochemical localization of growth factors in fetal wound healing, Dev. Biol. 147: 207 (1991).
S. Werner, K.G. Peters, M.T. Longaker, F. Fuller-Pace, M.J. Bander, and L.T. Williams, Large induction of keratinocyte growth factor expression in the dermis during wound healing, Proc. Natl. Acad. Sci. USA. 89: 6896, 1992.
S.E. Lynch, R.B. Colvin, and H.N. Antoniades, Growth factors in wound healing: single and synergistic effects on partial thickness porcine skin wounds, J. Clin. Invest. 84: 640 (1989).
B. Vogelstein, and K.W. Kinzler, p53 function and dysfunction, Cell 70: 523 (1992).
S.J. Ullrich, C.W. Anderson, W.E. Mercer, and E. Appella, The p53 tumor suppressor protein, a modulator of cell proliferation, J. Biol. Chem. 267: 15259 (1992).
G.P. Zambetti, and A.J. Levine, A comparison of the biological activities of wild-type and mutant p53, FASEB J. 7: 855 (1993).
H.N. Antoniades, M.A. Bravo, R.E. Avila, T. Galanopoulos, J. Neville-Golden, M. Maxwell, and M. Selman, Platelet-derived growth factor in idiopathic pulmonary fibrosis, J. Clin. Invest. 86: 1055 (1990).
H.N. Antoniades, T. Galanopoulos, J. Neville-Golden, and C.J. O’Hara, Malignant epithelial cells in primary human lung carcinomas co-express in vivo platelet-derived growth factor (PDGF) and PDGF receptor mRNAs and their protein products, Proc. Natl. Acad. Sci. USA. 89: 3942 (1992).
C.C. Chung, and H.N. Antoniades, Expression of c-sis/platelet-derived growth factor B, insulin-like growth factor I, and transforming growth factor a messenger RNAs and their respective receptor messenger RNAs in primary gastric carcinomas: In vivo studies with in situ hybridization and immunocytochemistry, Cancer Res. 52: 3453 (1992).
M. Xiao, T. Galanopoulos, J. Neville-Golden, J.P. Richie, and H.N. Antoniades, Human prostate adenocarcinomas express in vivo mRNA and protein products for platelet-derived growth factor B and its receptor, Int. J. Oncol. in press.
P. McL Black, Brain tumors, N. Eng. J. Med. 324: 1471 (1991).
S.K. Clinton, and P. Libby, Cytokines and growth factors in atherogenesis, Arch. Pathol. Lab. Med. 116: 1292 (1992).
R. Ross, The pathogenesis of atherosclerosis: a perspective for the 1990s, Nature 362: 801 (1993).
H.F. Dvorak, Tumors: wounds that do not heal, N. Eng. J. Med. 315: 1650 (1986).
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Antoniades, H.N. (1994). Chronic Cellular Injury and Human Proliferative Disorders. In: Maragoudakis, M.E., Gullino, P.M., Lelkes, P.I. (eds) Angiogenesis. NATO ASI Series, vol 263. Springer, Boston, MA. https://doi.org/10.1007/978-1-4757-9188-4_25
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DOI: https://doi.org/10.1007/978-1-4757-9188-4_25
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