Variations in the expression of platelet-derived endothelial cell growth factor in human colorectal polyps
Tóm tắt
Platelet-derived endothelial cell growth factor (PD-ECGF) has been identified to be an angiogenic factor, and a close relationship between the expression of PD-ECGF and tumor development has been postulated. This study was designed to assess both the role of PD-ECGF in human colorectal polyps as well as its relationship to the expression of other oncogenes during colorectal carcinogenesis. One hundred twenty patients with colon polyps who had undergone a polypectomy were studied. The polyps were classified based on the pathological findings as nonneoplastic or sporadic adenoma. The polyps were immunostained for PD-ECGF and vascular endothelial cell growth factor (VEGF), as well as for Ki-67 antigen and p53. The correlations between expression of PD-ECGF and clinicopathologic factors were examined. PD-ECGF was expressed at significant levels only in adenomas: in 4 of the 20 polyps with severe dysplasia (20%), and in 5 of the 20 cases of carcinoma in adenoma (25%). PDECGF was not detected in the nonneoplastic polyps and in adenomas with low-grade dysplasia. The intensity of immunostaining for PD-ECGF in adenomas correlated with the expression of Ki-67 antigen (P , 0.001) but not with that of p53. VEGF was not detected in any types of polyps. Angiogenic factors in colorectal adenomas might play an important role in carcinogenesis. The correlated expression of PD-ECGF and Ki-67 antigen suggests that PD-ECGF might not only act as an angiogenic factor, but also as a tumor growth factor.
Tài liệu tham khảo
Fidler IJ (1990) Critical factors in the biology of human cancer metastasis: twenty-eighth GHA Clowes memorial award lecture. Cancer Res 50:6130–6138
Liotta LA, Steeg PS, Stetler-Stevenson WG (1991) Cancer metastasis and angiogenesis: an imbalance of positive and negative regulation. Cell 64:327–336
Weidner N, Semple JP, Welch WR, Folkman J (1991) Tumor angiogenesis and metastasis — correlation in invasive breast carcinoma. N Engl J Med 324:1–8
Paley PJ, Staskus KA, Gebhard K, Mohanraj D, Twiggs LB, Carson LF, Ramakrishnan S (1997) Vascular endothelial growth factor expression in early stage ovarian carcinoma. Cancer 80:98–106
Tanigawa N, Amaya H, Matsumura M, Shimomatsuya T (1997) Correlation between expression of vascular endothelial growth factor and tumor vascularity, and patient outcome in human gastric carcinoma. J Clin Oncol 15:826–832
Potgens AJG, Westphal HR, de Waal RMW, Ruiter DJ (1995) The role of vascular permeability factor and basic fibroblast growth factor in tumor angiogenesis. Biol Chem Hoppe-Seyler 376:57–70
Schreiber AB, Winkler ME, Derynck R (1986) Transforming growth factor-alpha: a more potent angiogenic mediator than epidermal growth factor. Science 232:1250–1253
Koch AE, Polverini PJ, Kunkel SL, Harlow LA, DiPietro LA, Elner VM, Elner SG, Strieter RM (1992) Interleukin-8 as a macrophage-derived mediator of angiogenesis. Science 258:1798–1801
Leung DW, Cachianes G, Kuang WJ, Goeddel DV, Ferrara N (1989) Vascular endothelial growth factor is a secreted angiogenic mitogen. Science 246:1306–1309
Conn G, Bayne ML, Soderman DD, Kwok PW, Sullivan KA, Palisi TM, Hope DA, Thomas KA (1990) Amino acid and cDNA sequences of a vascular endothelial cell mitogen that is homologous to platelet-derived growth factor. Proc Natl Acad Sci USA 87:2628–2632
Sumizawa T, Furukawa T, Haraguchi M, Yoshimura A, Takeyasu A, Ishizawa M, Yamada Y, Akiyama S (1993) Thymidine phosphorylase activity associated with platelet-derived endothelial cell growth factor. J Biochem 114:9–14
Ishikawa F, Miyazono K, Hellman U, Drexler H, Wernstedt C, Hagiwara K, Usuki K, Takaku F, Risau W, Heldin CH (1989) Identification of angiogenic activity and the cloning and expression of platelet-derived endothelial cell growth factor. Nature 338:557–562
Haraguchi M, Miyadera K, Uemura K, Sumizawa T, Furukawa T, Yamada K, Akiyama S, Yamada Y (1994) Angiogenic activity of enzymes. Nature 368:198
Maeda K, Chung YS, Ogawa Y, Takatsuka S, Kang SM, Ogawa M, Sawada T, Onoda N, Kato Y, Sowa M (1996) Thymidine phosphorylase/platelet-derived endothelial cell growth factor expression associated with hepatic metastasis in gastric carcinoma. Br J Cancer 73:884–888
Takebayashi Y, Akiyama S, Akiba S, Yamada K, Miyadera K, Sumizawa T, Yamada Y, Murata F, Aikou T (1996) Clinicopathologic and prognostic significance of an angiogenic factor, thymidine phosphorylase, in human colorectal carcinoma. J Natl Cancer Inst 88:1110–1117
Vogelstein B, Fearon ER, Hamilton SR, Kern SE, Preisinger AC, Leppert M, Nakamura Y, White R, Smits AM, Bos JL (1988) Genetic alterations during colorectal-tumor development. N Engl J Med 319:525–532
Fearon ER, Vogelstein B (1990) A genetic model for colorectal tumorigenesis. Cell 61:759–767
Konishi F, Morson BC (1982) Pathology of colorectal adenomas: a colonoscopic survey. J Clin Pathol 35:830–841
Nishida M, Hino A, Mori K, Matsumoto T, Yoshikubo T, Ishitsuka H (1996) Preparation of anti-human thymidine phosphorylase monoclonal antibodies useful for detecting the enzyme levels in tumor tissues. Biol Pharm Bull 19:1407–1411
Ferrara N, Houck KA, Jakeman LB, Winer J, Leung DW (1991) The vascular endothelial growth factor family of polypeptides. J Cell Biochem 47:211–218
Gerdes J, Li L, Schlueter C, Duchrow M, Wohlenberg C, Gerlach C, Stahmer I, Kloth S, Brandt E, Flad HD (1991) Immunobiochemical and molecular biologic characterization of the cell proliferation-associated nuclear antigen that is defined by monoclonal antibody Ki-67. Am J Pathol 138:867–873
Banks L, Matlashewski G, Crawford K (1986) Isolation of humanp53-specific monoclonal antibodies and their use in the studies of human p53 expression. Eur J Biochem 159:529–534
Hsu SM, Raine L, Fanger H (1981) 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 75:734–738
Jiang SX, Sato Y, Kuwao S, Kameya T (1995) Expression of bcl-2 oncogene protein is prevalent in small cell lung carcinomas. J Pathol 177:135–138
Fox SB, Moghaddam A, Westwood M, Turley H, Bicknell R, Gatter KC, Harris AL (1995) Platelet-derived endothelial cell growth factor/thymidine phosphorylase expression in normal tissues: an immunohistochemical study. J Pathol 176:183–190
Hanahan D, Folkman J (1996) Patterns and emerging mechanisms of the angiogenic switch during tumorigenesis. Cell 86:353–364
Aotake T, Lu CD, Chiba Y, Muraoka R, Tanigawa N (1999) Changes of angiogenesis and tumor cell apoptosis during colorectal carcinogenesis. Clin Cancer Res 5:135–142
Moghaddam A, Zhang HT, Fan TD, Hu DE, Lees VC, Turley H, Fox S, Gatter KC, Harris AL, Bicknell R (1995) Thymidine phosphorylase is angiogenic and promotes tumor growth. Proc Natl Acad Sci USA 92:998–1002
Matsushita S, Nitanda T, Furukawa T, Sumizawa T, Tani A, Nishimoto K, Akiba S, Miyadera K, Fukushima M, Yamada Y, Yoshida H, Kanzaki T, Akiyama S (1999) The effect of a thymidine phosphorylase inhibitor on angiogenesis and apoptosis in tumors. Cancer Res 59:1911–1916
Fox SB, Westwood M, Moghaddam A, Comley M, Turley H, Whitehouse RM, Bicknell R, Gatter KC, Harris AL (1996) The angiogenic factor platelet-derived endothelial cell growth factor/ thymidine phosphorylase is up-regulated in breast cancer epithelium and endothelium. Br J Cancer 73:275–280
Takebayashi Y, Yamada K, Miyadera K, Sumizawa T, Furukawa T, Kinoshita F, Aoki D, Okumura H, Yamada Y, Akiyama SI, Aikou T (1996) The activity and expression of thymidine phosphorylase in human solid tumours. Eur J Cancer 32:1227–1232
Yoshimura A, Kuwazuru Y, Furukawa T, Yoshida H, Yamada K, Akiyama S (1990) Purification and tissue distribution of human thymidine phosphorylase; high expression in lymphocytes, reticulocytes and tumors. Biochim Biophys Acta 1034:107–113
Cavaillon JM (1994) Cytokines and macrophages. Biomed Pharmacother 48:445–453
Pyke C, Ralfkiaer E, Tryggvason K, Dano K (1993) Messenger RNA for two type IV collagenases is located in stromal cells in human colon cancer. Am J Pathol 142:359–365
Leek RD, Landers R, Fox SB, Ng F, Harris AL, Lewis CE (1998) Association of tumour necrosis factor alpha and its receptors with thymidine phosphorylase expression in invasive breast carcinoma. Br J Cancer 77:2246–2251
