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Involvement of platelet-derived growth factor ligands and receptors in tumorigenesis
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Medical Biochemistry and Microbiology.ORCID iD: 0000-0002-9508-896x
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Medicinska och farmaceutiska vetenskapsområdet, centrumbildningar mm, Ludwig Institute for Cancer Research. Uppsala University, Science for Life Laboratory, SciLifeLab. Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Pharmacy, Department of Pharmaceutical Biosciences.
Uppsala University, Disciplinary Domain of Medicine and Pharmacy, Faculty of Medicine, Department of Immunology, Genetics and Pathology.
2018 (English)In: Journal of Internal Medicine, ISSN 0954-6820, E-ISSN 1365-2796, Vol. 283, no 1, p. 16-44Article, review/survey (Refereed) Published
Abstract [en]

Platelet-derived growth factor (PDGF) isoforms and their receptors have important roles during embryogenesis, particularly in the development of various mesenchymal cell types in different organs. In the adult, PDGF stimulates wound healing and regulates tissue homeostasis. However, overactivity of PDGF signalling is associated with malignancies and other diseases characterized by excessive cell proliferation, such as fibrotic conditions and atherosclerosis. In certain tumours, genetic or epigenetic alterations of the genes for PDGF ligands and receptors drive tumour cell proliferation and survival. Examples include the rare skin tumour dermatofibrosarcoma protuberance, which is driven by autocrine PDGF stimulation due to translocation of a PDGF gene, and certain gastrointestinal stromal tumours and leukaemias, which are driven by constitute activation of PDGF receptors due to point mutations and formation of fusion proteins ofthe receptors, respectively. Moreover, PDGF stimulates cells in tumour stroma and promotes angiogenesis as well as the development of cancer-associated fibroblasts, both of which promote tumour progression. Inhibitors of PDGF signalling may thus be of clinical usefulness in the treatment of certain tumours.

Place, publisher, year, edition, pages
2018. Vol. 283, no 1, p. 16-44
Keywords [en]
inhibitor, kinase, malignancy, receptor, signal transduction, PDGF
National Category
Cell and Molecular Biology Cell Biology
Identifiers
URN: urn:nbn:se:uu:diva-347709DOI: 10.1111/joim.12690ISI: 000418411100002PubMedID: 28940884OAI: oai:DiVA.org:uu-347709DiVA, id: diva2:1195752
Funder
Swedish Cancer Society, 2016/445; 2015/226; 2014/468Swedish Research Council, 2015-02757Available from: 2018-04-06 Created: 2018-04-06 Last updated: 2018-04-06Bibliographically approved

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Heldin, Carl-HenrikLennartsson, JohanWestermark, Bengt

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Ludwig Institute for Cancer ResearchScience for Life Laboratory, SciLifeLabDepartment of Medical Biochemistry and MicrobiologyDepartment of Pharmaceutical BiosciencesDepartment of Immunology, Genetics and Pathology
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Journal of Internal Medicine
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