Журнал канцерогенеза и мутагенеза

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Epidermal Growth Factor (EGF) and Platelet-Derived Growth Factor (PDGF) as Tissue Healing Agents: Clarifying Concerns about their Possible Role in Malignant Transformation and Tumor Progression

Jorge Berlanga-Acosta, Jorge Gavilondo-Cowley, Diana García del Barco-Herrera, Jorge Martín-Machado and Gerardo Guillen-Nieto

EGF and PDGF, reminiscent of the early hopes of solution for problem wounds have attained a niche by healing diabetic ulcers. Although they belong to unrelated families, multiple biological features are shared. Mounting evidences reviewed here; document however, divergent and opposing roles for EGF and PDGF in both tissue repair and tumorigenesis. Wounds: As EGF receptor is not expressed by inflammatory cells, its ligand does not quantitatively or qualitatively modifies the course of inflammation. In contrast, PDGFB recruits and perpetuates inflammation. These infiltrated inflammatory cells turns and additional local source of growth factors. EGF enhances matrix synthesis via gene expression, while PDGF increases wound fibroblasts and myofibroblasts population density and exhibits far more chemotactic and angiogenic effect. Epithelialization is distinctly stimulated by EGF. Oncogenesis: EGF is not an oncogene-derived product and does not render perpetual or irreversible transformation in vitro or in vivo. Its promoting effect is not uniformly reproduced and seems to depend upon the animals genetic background, targeted tissue biology, and/or the chemical carcinogen-induced mutations. A variety EGF receptor mutated forms may confer cell’s self-sufficiency for no need of exogenousgrowth factors supply. PDGFB is an oncogen product, establishes growth-perpetuating autocrine loops and confers self-sufficiency to glial tumorigenesis. Its role as a co-carcinogen as in tumor stroma and neoangiogenesis appears far more defined. Understanding the cellular and molecular imprinting of EGF and PDGF would allow for the judicious medical balance in terms of risk-benefit for the patient.