title: Cytokines associated with the pathophysiology of aggressive fibromatosis.
abstract: The rare benign extra-abdominal desmoid tumor is characterized by aggressive invasion of normal tissue. Treatment is complicated by its recurrence, invasiveness, and persistence. The etiology is unknown and the pathophysiology is obscure. Because of exuberant fibroblastic proliferation with collagenous tissue being the primary tissue component, this desmoid tumor has been compared with keloids arising from excessive scar formation in healing wounds. Numerous cytokines are associated with signaling for growth and maintenance of mesenchymal cells. Altered expression of these proteins is associated with many pathologic conditions. It has been proposed that the enhanced expression of platelet-derived growth factor and its receptor characterize desmoid tumors. We tested the hypothesis that the exuberant fibrosis of desmoid tumors may have resulted from the initiation of the cascade of molecular events producing increased expression of cytokines. We used immunohistochemical analysis of cytokines in desmoid tumors compared with keloids and skin to localize the expression of cytokines. The results showed localized increased expression of the cytokines epidermal growth factor, transforming growth factor-beta, tumor necrosis factor-alpha, vascular endothelial growth factor, interleukin-1beta, and interleukin-6 in the endothelial cells of blood vessels in the tumors. Production of tumor necrosis factor-alpha and interleukin-1beta in tumor tissue was increased, but we did not find increased expression of platelet-derived growth factor. We concluded that the increased expression of cytokines associated with angiogenesis usually found in wound healing and invasive tumors may contribute to the pathophysiology of the desmoid tumor.
authors.affiliation: Department of Basic Sciences, School of Dentistry, University of Southern California, Los Angeles, USA. bmills@hsc.usc.edu
authors.forename: B G
authors.initials: BG
authors.lastname: Mills
authors.forename: A
authors.initials: A
authors.lastname: Frausto
authors.forename: E
authors.initials: E
authors.lastname: Brien
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D016228:Endothelial Growth Factors / Q000032:analysis / Q000096:biosynthesis; D004815:Epidermal Growth Factor / Q000032:analysis / Q000096:biosynthesis; D066246:ErbB Receptors / Q000032:analysis / Q000096:biosynthesis; D005260:Female; D016220:Fibroblast Growth Factor 1 / Q000032:analysis / Q000096:biosynthesis; D016222:Fibroblast Growth Factor 2 / Q000032:analysis / Q000096:biosynthesis; D018222:Desmoid Tumors / Q000378:metabolism* / Q000503:physiopathology*; D006801:Humans; D007375:Interleukin-1 / Q000032:analysis / Q000096:biosynthesis*; D015850:Interleukin-6 / Q000032:analysis / Q000096:biosynthesis*; D008222:Lymphokines / Q000032:analysis / Q000096:biosynthesis; D008297:Male; D010982:Platelet-Derived Growth Factor / Q000032:analysis / Q000096:biosynthesis; D017468:Receptors, Fibroblast Growth Factor / Q000032:analysis / Q000096:biosynthesis; D019947:Receptors, Interleukin-6 / Q000032:analysis / Q000096:biosynthesis; D017479:Receptors, Platelet-Derived Growth Factor / Q000032:analysis / Q000096:biosynthesis; D019030:Receptors, Vitronectin / Q000032:analysis / Q000096:biosynthesis; D012983:Soft Tissue Neoplasms / Q000378:metabolism* / Q000503:physiopathology*; D016211:Transforming Growth Factor alpha / Q000032:analysis / Q000096:biosynthesis; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors
chemical_list: D016228:Endothelial Growth Factors; D007375:Interleukin-1; D015850:Interleukin-6; D008222:Lymphokines; D010982:Platelet-Derived Growth Factor; D017468:Receptors, Fibroblast Growth Factor; D019947:Receptors, Interleukin-6; D019030:Receptors, Vitronectin; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; D017479:Receptors, Platelet-Derived Growth Factor