Tumor secretion of growth factors.
An increasing number of polypeptide growth factors have been identified that regulate not only cell proliferation but also an extraordinary range of cell activities, including matrix protein deposition and resolution, the maintenance of cell viability, cell differentiation, inflammation, and tissue repair. Normal cells appear to require growth factors for proliferation and for maintenance of viability. Cells that secrete a polypeptide growth factor have an advantage in growth. These factors can act either externally through cell surface receptors or internally during the transport of receptors and growth factors through the endoplasmic reticulum and Golgi apparatus, causing autocrine stimulation of cell growth. Depending on the cell type, growth factors can also be potent inhibitors of cell growth rather than stimulators of growth, and the effect can depend on the presence or absence of growth factors. Among the growth factors considered, IGFs are unusual in that they function both as endocrine and as autocrine/paracrine agents. IGF-II, which is associated with fetal growth, is the IGF most frequently expressed by tumors. There is now convincing evidence that some tumors secrete sufficient IGF-II to have systemic endocrine effects as recognized as nonislet cell tumor hypoglycemia. PDGF is normally highly concentrated in platelets and has major significance in stimulation of cellular proliferation in inflammation and wound repair. Normally, this proliferation is self-limited, but the secretion of PDGF by tumors and its effects on cell proliferation of tumors persist. The fact that PDGF B monomer has an identical structure with that of the proto-oncogene C-cis further strengthens the connection between PDGF and tumor growth. EGF has a restricted role in normal physiology, but its close relative, TGF-alpha, is widely distributed in normal and neoplastic tissues. The common receptor for EGF and TGF-alpha is present in many normal and neoplastic cell types. The EGF receptor is the product of the C-erb gene. The oncogene V-cis is a truncated form of the EGF receptor whose tyrosine kinase activity is not dependent on ligand binding. TGF-beta exists in multiple forms. Although it can transform the morphology of certain cell lines in culture, it probably does not act generally as a mitogenic agent. Its major physiologic role in the body appears to be the stimulation of mesenchymal matrix formation. It is of special importance in the regulation of bone matrix formation. Its expression is increased in many tumors.(ABSTRACT TRUNCATED AT 400 WORDS)
Daughaday
W H
WH
Department of Medicine, Washington University School of Medicine, St. Louis, Missouri.
Deuel
T F
TF
D002352:Carrier Proteins / Q000378:metabolism; D004815:Epidermal Growth Factor / Q000378:metabolism; D006133:Growth Substances / Q000378:metabolism*; D006729:Hormones, Ectopic / Q000378:metabolism*; D006801:Humans; D018969:Insulin-Like Growth Factor Binding Proteins; D009384:Paraneoplastic Endocrine Syndromes / Q000503:physiopathology*; D010982:Platelet-Derived Growth Factor / Q000235:genetics / Q000378:metabolism; D000090063:Proto-Oncogene Mas; D011956:Receptors, Cell Surface / Q000502:physiology; D017479:Receptors, Platelet-Derived Growth Factor; D017451:Receptors, Somatomedin; D013002:Somatomedins / Q000235:genetics / Q000378:metabolism; D016211:Transforming Growth Factor alpha / Q000378:metabolism; D016212:Transforming Growth Factor beta / Q000378:metabolism
D002352:Carrier Proteins; D006133:Growth Substances; D006729:Hormones, Ectopic; D018969:Insulin-Like Growth Factor Binding Proteins; C000715470:MAS1 protein, human; D010982:Platelet-Derived Growth Factor; D000090063:Proto-Oncogene Mas; D011956:Receptors, Cell Surface; D017451:Receptors, Somatomedin; D013002:Somatomedins; D016211:Transforming Growth Factor alpha; D016212:Transforming Growth Factor beta; D004815:Epidermal Growth Factor; D017479:Receptors, Platelet-Derived Growth Factor