epidermal-growth-factor and Parotid-Neoplasms

The interaction between tumor cells and surrounding normal cells is very important in the prognosis of tumors. The object of this study was to determine the effect of recipient bed of tumor xenograft on tumor metastasis using a novel parotid gland tumor model. HeLa cells were xenografted into the parotid gland or subcutaneous tissues of athymic mice. Eight weeks after the transplantation, all mice were euthanized and specimens were immunostained with antibodies for angiogenic factors. FGF-2 was given to HeLa cells and the effect on the cellular migration was determined. EGF was also given to HeLa cells for the evaluation of FGF-2 induction. Immunohistochemical staining was done for the vascular metastasis-related factors on 26 human salivary gland tumors. HeLa cells showed significantly higher lung metastatic potential in the parotid gland than in the subcutis. Immunohistochemical staining revealed overexpression of FGF-2 in the parotid tumors compared to the subcutaneous tumors. The application of FGF-2 to implanting HeLa cells increased the cellular invasion in a dose-dependent manner. The application of EGF increases FGF-2 expression in HeLa cells. In clinical specimens, EGF and VEGF signaling proteins were more expressed than in normal salivary glandular tissues. In conclusion, a parotid tumor model of HeLa cells was successfully developed and it closely mimics high metastasis. These results indicate that recipient bed with intense EGF expression increases tumor metastasis through upregulation of FGF-2 expression.

Topics: Animals; Carcinoma, Adenoid Cystic; Epidermal Growth Factor; ErbB Receptors; Fibroblast Growth Factor 2; HeLa Cells; Humans; Lung Neoplasms; Male; Mice; Mice, Nude; Neoplasm Transplantation; Parotid Neoplasms; Transplantation, Heterologous; Xenograft Model Antitumor Assays

Saliva provides a natural reservoir of growth factors whose purposes have remained elusive. Animal studies suggest that saliva-derived growth factors play a role in systemic and oral wound healing. In the current study, salivary concentrations of epidermal growth factor (EGF) were monitored in patients before and after oral and juxtaoral surgery.. Whole resting saliva was collected from a group of patients with parotid gland tumors requiring surgical resection. Another group of patients a history of periodontal disease requiring surgical intervention also provided whole salivary samples. Healthy age- and sex-matched persons served as controls.. Salivary EGF levels were elevated in both groups of patients within 24 hours after surgery. In the periodontitis patients, a second smaller peak was assayed noted between 36 and 48 hours. After this, EGF concentrations returned to levels comparable to healthy controls in both experimental groups.. Although the local cells have the ability to synthesize and secrete growth factors at a site of injury, these results suggest that surgery stimulates increased synthesis and secretion of growth factors in the saliva as well. This increased level of saliva-derived growth factor may also aid in promoting wound healing.

Topics: Adult; Aged; Analysis of Variance; Case-Control Studies; Epidermal Growth Factor; Female; Follow-Up Studies; Humans; Linear Models; Logistic Models; Male; Middle Aged; Parotid Neoplasms; Periodontitis; Saliva; Spectrophotometry; Wound Healing

Human parotid tumors were evaluated for the activation of the phosphotyrosine signaling pathway by Western blot, enzyme activity assay, and reverse transcriptase-polymerase chain reaction. Warthin's tumor and mucoepidermoid carcinomas had the greatest level of tyrosine phosphorylated proteins identified in plasma membrane fractions. These tumors, along with pleomorphic adenocarcinoma, showed high levels of membrane expression of the tyrosine kinase receptor, c-erbB-2, and phosphatidylinositol-3-kinase. Expression of the epidermal growth factor receptor was confined to normal tissue. The level of mRNA for c-erb was elevated only in mucoepidermoid carcinomas. Messenger RNA levels for ras were unchanged from control levels in all tumors, while the level of src mRNA was higher in the tumor samples than the normal parotid tissue. The activities of several signal transduction kinases, including protein kinase A and C were elevated in tumor tissue (7.7- to 18.9- and 0.4- to 3.7-fold higher, respectively), relative to surrounding normal tissue. While the level of glandular amylase was reduced (22%-0% of normal levels) in the tumor tissue, epidermal growth factor (EGF) and transforming growth factor-alpha (TGFalpha) content was dramatically higher in the neoplastic tissue (10- to 170-fold and 4.6- to 6.0-fold, respectively). These results suggest that with the presence of elevated levels of EGF, TGFalpha, and the oncoprotein receptor c-erbB-2 in the membrane of parotid tumors, cell proliferation and activation of the phosphotyrosine signal transduction pathway may involve autocrine stimulation through the expression of high levels of growth factor and receptor in the same tissue.

Topics: Base Sequence; Cyclic AMP-Dependent Protein Kinases; Epidermal Growth Factor; Humans; Molecular Sequence Data; Parotid Neoplasms; Phosphotyrosine; Polymerase Chain Reaction; Protein Kinase C; Receptor, ErbB-2; RNA, Messenger; Signal Transduction; Transforming Growth Factor alpha

Several physiological parameters were examined for inducing acinar cell proliferation and corresponding increased expression of beta 1-4 galactosyltransferase. In this study, dietary changes causing acinar cell proliferation included the following: the introduction of animals to a liquid diet (causing gland atrophy) followed by re-introduction of solid chow, gustatory stimulation provided by the introduction of 0.5% citric acid to animal drinking water, and removal of the submandibular gland with subsequent reliance on the parotid gland for saliva protein and fluid. Alterations in growth factor levels were produced by injecting animals with a chronic (three-day) regimen of either nerve growth factor (NGF) or epidermal growth factor (EGF). In all cases of acinar cell proliferation in vivo, generated by the above treatments, cell-surface galactosyltransferase was detected along with the unique expression of a 4.5-kb proliferation-associated mRNA. Parotid gland proliferation could be blocked in all cases by the injection of the galactosyltransferase specific modifier protein, alpha-lactalbumin. Propranolol, a beta-adrenergic receptor antagonist, blocked proliferation in all cases except EGF treatment. EGF-induced proliferation could, however, be prevented if the animals were treated with monoclonal antibody to EGF receptor or with the galactosyltransferase modifier alpha-lactalbumin. As a comparison, human parotid tissue samples obtained from neoplastic pleomorphic adenomas, muco-epidermoid carcinoma, adenoid cystic carcinoma, and a bulimia patient were analyzed for galactosyltransferase expression by Northern blot of mRNA and plasma membrane isolation. Elevated levels of galactosyltransferase were found in all neoplastic tissue preparations as well as in the bulimia sample. Amylase synthesis was reduced in samples compared with surrounding normal tissue from the same patient. In vitro cell culturing of pleomorphic adenoma cells in the presence of galactosyltransferase modifier alpha-lactalbumin and substrate UDP-galactose inhibited proliferation in a dose-dependent fashion. Southern blot analysis of DNA from neoplastic parotid cells showed an alteration in chromosomal gene structure for the galactosyltransferase activator cDNA from the adenoid cystic carcinoma. These results for induced acinar cell proliferation as well as human neoplastic pathologies suggest a direct role for cell surface beta 1-4 galactosyltransferase in signaling growth. Furthermore, the

Topics: Animals; Bulimia; Cell Division; Epidermal Growth Factor; Galactosyltransferases; Humans; Hyperplasia; Hypertrophy; Lactalbumin; Membrane Proteins; Nerve Growth Factors; Parotid Gland; Parotid Neoplasms; Propranolol; Rats