Abstract
In this study we examined the expression of platelet‐derived growth factor (PDGF) A‐chain and PDGF receptor genes in seven human gastric carcinoma cell lines and 15 gastric carcinoma tissues. Expression of mRNA for PDGF A‐chain was found in all gastric cell lines and all gastric carcinoma tissues. Two of the seven gastric carcinoma cell lines expressed PDGF receptor mRNA. Out of the 15 gastric carcinoma tissues, eight showed enhanced expression of PDGF receptor mRNA and all of them demonstrated prominent fibrous stroma. Moreover, the incidence of enhanced expression of PDGF receptor mRNA was higher in scirrhous carcinoma than in well differentiated adenocarcinoma. These results strongly suggest that PDGF produced by tumor cells acts as a paracrine growth factor for production of fibrous stroma in gastric carcinomas
Keywords: PDGF, PDGF receptor, Gastric carcinoma
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REFERENCES
- 1. ) Ross , R. , Raines , E. W. and Bo wen‐Pope , D. F.The biology of platelet‐derived growth factor . Cell , 46 , 155 – 169 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 2. ) Heldin , C‐H , and Westermark , B.Role of PDGF‐like growth factor in autocrine stimulation of growth of normal and transformed cells . In “ Oncogenes and Growth Control ,” ed. Kahn P. and Graf T. , pp. 43 – 50 ( 1986. ). Springer‐Verlag; , Berlin, Heidelberg ). [Google Scholar]
- 3. ) Antoniades , H. N. and Hunkapiller , M. W.Human platelet‐derived growth factor (PDGF): amino‐terminal amino acid sequence . Science , 220 , 963 – 965 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 4. ) Betsholotz , C. , Johnsson , A. , Heldin , C‐H. , Westermark , B. , Lind , P. , Urdea , M. S. , Eddy , R. , Shows , T. B. , Philpott , K. , Mellor , A. L. , Knott , T. J. and Scott , J.cDNA sequence and chromosomal localization of human platelet‐derived growth factor A‐chain and its expression in tumour cell lines . Nature , 320 , 695 – 699 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 5. ) Doolittle , R. F. , Hunkapiller , M. W. , Hood , L. E. , Devare , S. G. , Robbins , K. C. , Aaronson , S. A. and Antoniades , H. N.Simian sarcoma virus onc gene, v‐sis, is derived from the gene (or genes) encoding a platelet‐derived growth factor . Science , 221 , 275 – 277 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 6. ) Waterfield , M. D. , Scrace , G. T. , Whittle , N. , Stroobant , P. , Johnsson , A. , Wasteson , A. , Westermark , B. , Heldin , C‐H. , Huang , J. S. and Deuel , T. F.Platelet‐derived growth factor is structurally related to the putative transforming protein p28sis of simian sarcoma virus . Nature , 304 , 35 – 39 ( 1983. ). [DOI] [PubMed] [Google Scholar]
- 7. ) Swan , D. C , McBride , O. W. , Robbins , K. C. , Keithey , D. A. , Reddy , E. P. and Aaronson , S. A.Chromosomal mapping of the simian sarcoma virus one gene analogue in human cells . Proc. Natl. Acad. Sci. USA , 79 , 4691 – 4695 ( 1982. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 8. ) Dalla‐Favera , R. , Gallo , R. C. , Giallongo , A. and Croce , C. M.Chromosomal localization of the human homolog (c‐sis) of the simian sarcoma virus one gene . Science , 218 , 686 – 688 ( 1982. ). [DOI] [PubMed] [Google Scholar]
- 9. ) Bishayee , S. , Ross , A. H. , Womer , R. and Scher , C. D.Purified human platelet‐derived growth factor receptor has ligand‐stimulated tyrosine kinase activity . Proc. Natl, Acad. Sci. USA , 83 , 6756 – 6760 ( 1986. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 10. ) Gronwald , R. G. K. , Grant , F. J. , Haldeman , B. A. , Hart , C. E. , O'Hara , P. J. , Hagen , F. S. , Ross , R. , Bowen‐Pope , D. F. and Murray , M. J.Cloning and expression of a cDNA coding for the human platelet‐derived growth factor receptor: evidence for more than one receptor class . Proc. Natl. Acad. Sci. USA , 85 , 3435 – 3439 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 11. ) Yarden , Y. , Escobedo , J. A. , Kuang , W‐J. , Yang‐Feng , T. L. , Daniel , T. O. , Tremble , P. M. , Chen , E. Y. , Ando , M. E. , Harkins , R. N. , Francke , U , Fried , V. A , Ullrich , A. and Williams , L. T.Structure of the receptor for platelet‐derived growth factor helps define a family of closely related growth factor receptors . Nature , 323 , 226 – 232 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 12. ) Roberts , W. M. , Look , A. T. , Roussel , M. F. and Sherr , C. J.Tandem linkage of human CSF‐1 receptor (c‐fms) and PDGF receptor genes . Cell , 55 , 655 – 661 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 13. ) Versnel , M. A. , Hagemeijer , A. , Bouts , M. J. , van der Kwast , T. H. and Hoogsteden , H. C.Expression of c‐sis (PDGF B‐chain) and PDGF A‐chain genes in ten human malignant mesothelioma cell lines derived from primary and metastatic tumors . Oncogene , 2 , 601 – 605 ( 1988. ). [PubMed] [Google Scholar]
- 14. ) Hermansson , M. , Nistér , M. , Betsholtz , C. , Heldin , C‐H. , Westermark , B , and Funa , K.Endothelial cell hyperplasia in human glioblastoma: coexpression of mRNA for platelet‐derived growth factor (PDGF) B chain and PDGF receptor suggests autocrine growth stimulation . Proc. Natl. Acad. Sci. USA , 85 , 7748 – 7752 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 15. ) Söderdahl , G. , Betsholtz , C. , Johansson , A. , Nilsson , K. and Bergh , J.Differential expression of platelet‐derived growth factor and transforming growth factor genes in small‐ and non‐small‐cell human lung carcinoma cells . Int. J. Cancer , 41 , 636 – 641 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 16. ) Bronzert , D. A. , Pantazis , P. , Antoniades , H. N. , Kasid , A. , Davidson , N. , Dickson , R. B. and Lippman , M. E.Synthesis and secretion of platelet‐derived growth factor by human breast cancer cell lines . Proc. Natl. Acad. Sci. USA , 84 , 5763 – 5767 ( 1987. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 17. ) Peres , R. , Betsholtz , C. , Westermark , B. and Heldin , C‐H.Frequent expression of growth factors for mesenchymal cells in human mammary carcinoma cell lines . Cancer Res. , 47 , 3425 – 3429 ( 1987. ). [PubMed] [Google Scholar]
- 18. ) Sariban , E. and Kufe , D.Expression of the platelet‐derived growth factor 1 and 2 genes in human myeloid cell lines and monocytes . Cancer Res. , 48 , 4498 – 4502 ( 1988. ). [PubMed] [Google Scholar]
- 19. ) Heldin , N‐E. , Gustavsson , B. , Claesson‐Welsh , L. , Hammacher , A. , Mark , J. , Heldin , C‐H. and Westermark , B.Aberrant expression of receptors for platelet‐derived growth factor in an anaplastic thyroid carcinoma cell line . Proc. Natl. Acad. Sci. USA , 85 , 9302 – 9306 ( 1988. ). [DOI] [PMC free article] [PubMed] [Google Scholar]
- 20. ) Gazit , A. , Igarashi , H. , Chiu , I‐M. , Srinivasan , A. , Yaniv , A. , Tronick , S. R. , Robbins , K. C. and Aaronson , S. A.Expression of the normal human sis/PDGF‐2 coding sequence induces cellular transformation . Cell , 39 , 89 – 97 ( 1984. ). [DOI] [PubMed] [Google Scholar]
- 21. ) Heldin , C‐H. , Johnsson , A. , Wennergren , S. , Wernstedt , C. , Betsholz , C. and Westermark , B. Ahuman osteosar‐coma cell line secretes a growth factor structurally related to a homodimer of PDGF A‐chains . Nature , 319 , 511 – 514 ( 1986. ). [DOI] [PubMed] [Google Scholar]
- 22. ) Nistér , M. , Hammacher , A. , Mellström , K. , Siegbahn , A. , Rönnstrand , L. , Westermark , B. and Heldin , C‐H.A gliomaderived PDGF A chain homodimer has different functional activities from a PDGF AB heterodimer purified from human platelets . Cell , 52 , 791 – 799 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 23. ) Hart , C. E. , Forstrom , J. W. , Kelly , J. D. , Seifert , R. A. , Smith , R. A. , Ross , R. , Murray , M. J. and Bowen‐Pope , D. F.Two classes of PDGF receptor recognize different isoforms of PDGF . Science , 240 , 1529 – 1531 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 24. ) Escobedo , J. A. , Navankasatussas , S. , Cousens , L. S. , Coughlin , S. R. , Bell , G. I. and Williams , L. T. Acommon PDGF receptor is activated by homodimeric A and B forms of PDGF . Science , 240 , 1532 – 1534 ( 1988. ). [DOI] [PubMed] [Google Scholar]
- 25. ) Bergh , J.The expression of the platelet‐derived growth factor genes in human nonsmall lung cancer cell lines is related to tumor stroma formation in nude mice . Am. J. Pathol. , 133 , 434 – 439 ( 1988. ). [PMC free article] [PubMed] [Google Scholar]
- 26. ) Yoshida , K. , Takanashi , A. , Kyo , E. , Ito , M. , Ito , H. , Niimoto , M. , Hattori , T. and Tahara , E.Epidermal growth factor induces the expression of its receptor gene in human gastric carcinoma cell line TMK‐1 . Jpn. J. Cancer Res. , 80 , 743 – 746 ( 1989. ). [DOI] [PMC free article] [PubMed] [Google Scholar]