Expression of Platelet-derived Growth Factor and Its Receptors in Proliferative Disorders of Fibroblastic Origin

Overview

Journal Am J Pathol

Publisher Elsevier

Specialty Pathology

Date 1992 Mar 1

PMID 1372158

Citations 19

Authors

A Smits

K Funa

F S Vassbotn

F af Ekenstam

C H Heldin

B Westermark

M Nister

Affiliations

Soon will be listed here.

Abstract

Platelet-derived growth factor (PDGF) is known to stimulate the proliferation of connective tissue-derived cells in vitro. Less is known about its functions in vivo, and the role of PDGF in the development of human tumors has not been clarified. The authors have investigated the occurrence of PDGF and PDGF receptors in a series of proliferative disorders of fibroblastic origin using immunohistochemical and in situ hybridization techniques. High expression of PDGF beta-receptor mRNA and protein was found in the malignant tumors, and also in some benign lesions, such as dermatofibroma. In all these cases, benign as well as malignant, the PDGF B-chain mRNA, and less clearly, the PDGF A-chain mRNA, were coexpressed with the beta-receptor. In contrast, high expression of PDGF alpha-receptor mRNA was only found in fully malignant lesions, i.e., malignant fibrous histiocytoma. These data indicate that an autocrine growth stimulation via the PDGF beta-receptor could occur in an early phase of tumorigenesis, and may be a necessary but insufficient event for the progression into fully malignant human connective tissue lesions.

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References

Katenkamp D, Stiller D, Schulze E . Ultrastructural cytology of regenerating tendon--an experimental study. Exp Pathol (Jena). 1976; 12(1):25-37. DOI: 10.1016/s0014-4908(76)80030-0. View

Heldin C, Westermark B . Growth factors: mechanism of action and relation to oncogenes. Cell. 1984; 37(1):9-20. DOI: 10.1016/0092-8674(84)90296-4. View

Claesson-Welsh L, Hammacher A, Westermark B, Heldin C, Nister M . Identification and structural analysis of the A type receptor for platelet-derived growth factor. Similarities with the B type receptor. J Biol Chem. 1989; 264(3):1742-7. View

Matsui T, Heidaran M, Miki T, Popescu N, La Rochelle W, Kraus M . Isolation of a novel receptor cDNA establishes the existence of two PDGF receptor genes. Science. 1989; 243(4892):800-4. DOI: 10.1126/science.2536956. View

Smits A, Hermansson M, Nister M, Karnushina I, Heldin C, Westermark B . Rat brain capillary endothelial cells express functional PDGF B-type receptors. Growth Factors. 1989; 2(1):1-8. DOI: 10.3109/08977198909069076. View

Pierce G, Mustoe T, Lingelbach J, Masakowski V, Griffin G, Senior R . Platelet-derived growth factor and transforming growth factor-beta enhance tissue repair activities by unique mechanisms. J Cell Biol. 1989; 109(1):429-40. PMC: 2115493. DOI: 10.1083/jcb.109.1.429. View

Gronwald R, Grant F, Haldeman B, Hart C, OHara P, Hagen F . 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 U S A. 1988; 85(10):3435-9. PMC: 280226. DOI: 10.1073/pnas.85.10.3435. View

Hermansson M, Nister M, Betsholtz C, Heldin C, Westermark B, 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 U S A. 1988; 85(20):7748-52. PMC: 282270. DOI: 10.1073/pnas.85.20.7748. View

Rubin K, Tingstrom A, Hansson G, Larsson E, Ronnstrand L, Klareskog L . Induction of B-type receptors for platelet-derived growth factor in vascular inflammation: possible implications for development of vascular proliferative lesions. Lancet. 1988; 1(8599):1353-6. DOI: 10.1016/s0140-6736(88)92177-0. View

10.

Sprugel K, McPherson J, Clowes A, Ross R . Effects of growth factors in vivo. I. Cell ingrowth into porous subcutaneous chambers. Am J Pathol. 1987; 129(3):601-13. PMC: 1899822. View

11.

Pantazis P, Pelicci P, Dalla-Favera R, Antoniades H . Synthesis and secretion of proteins resembling platelet-derived growth factor by human glioblastoma and fibrosarcoma cells in culture. Proc Natl Acad Sci U S A. 1985; 82(8):2404-8. PMC: 397566. DOI: 10.1073/pnas.82.8.2404. View

12.

Mohr W, Vossbeck G . [Proliferation and 3H proline incorporation of cells of palmar fibromatosis (Dupuytren disease)]. Z Rheumatol. 1985; 44(5):226-30. View

13.

Eva A, ROBBINS K, Andersen P, Srinivasan A, Tronick S, Reddy E . Cellular genes analogous to retroviral onc genes are transcribed in human tumour cells. Nature. 1982; 295(5845):116-9. DOI: 10.1038/295116a0. View

14.

Doolittle R, Hunkapiller M, HOOD L, Devare S, ROBBINS K, Aaronson S . Simian sarcoma virus onc gene, v-sis, is derived from the gene (or genes) encoding a platelet-derived growth factor. Science. 1983; 221(4607):275-7. DOI: 10.1126/science.6304883. View

15.

Bergstresser P, Tigelaar R, Tharp M . Conjugated avidin identifies cutaneous rodent and human mast cells. J Invest Dermatol. 1984; 83(3):214-8. DOI: 10.1111/1523-1747.ep12263584. View

16.

Heldin C, Westermark B . Platelet-derived growth factor: mechanism of action and possible in vivo function. Cell Regul. 1990; 1(8):555-66. PMC: 361590. DOI: 10.1091/mbc.1.8.555. View

17.

Vassbotn F, Langeland N, Hagen I, Holmsen H . A monoclonal antibody against PDGF B-chain inhibits PDGF-induced DNA synthesis in C3H fibroblasts and prevents binding of PDGF to its receptor. Biochim Biophys Acta. 1990; 1054(2):246-9. DOI: 10.1016/0167-4889(90)90248-c. View

18.

Ross R, Masuda J, Raines E, Gown A, Katsuda S, Sasahara M . Localization of PDGF-B protein in macrophages in all phases of atherogenesis. Science. 1990; 248(4958):1009-12. DOI: 10.1126/science.2343305. View

19.

Ronnstrand L, Terracio L, Claesson-Welsh L, Heldin C, Rubin K . Characterization of two monoclonal antibodies reactive with the external domain of the platelet-derived growth factor receptor. J Biol Chem. 1988; 263(21):10429-35. View

20.

Perosio P, Brooks J . Expression of growth factors and growth factor receptors in soft tissue tumors. Implications for the autocrine hypothesis. Lab Invest. 1989; 60(2):245-53. View