transforming-growth-factor-alpha and Sarcoma

Fifty feline sarcomas associated with vaccine-site injection were evaluated to determine the immunohistochemical expression of p53 protein, basic fibroblast growth factor (FGF-b), and transforming growth factor-alpha (TGF-alpha). Forty-one tumors (82%) were fibrosarcomas (FS), eight (16%) were malignant fibrous histiocytomas (MFH), and one (2%) was a chondrosarcoma (CS). Overexpression of p53 protein was observed in the nuclei of tumor cells in 28 (56%) sarcomas; FGF-b expression was found in the cytoplasm of tumor cells in 40 (80%) feline sarcomas, but the staining was more intense in the spindle-shaped cells of FS than in polygonal or round cells of MFH. The single CS faintly expressed FGF-b. The majority of feline vaccine-associated sarcomas (43 of 50, 86%) expressed moderate or intense staining for TGF-alpha in the cytoplasm of tumor cells. Heterogeneous immunolabeling for p53, FGF-b, and TGF-alpha was present in neoplastic, multinucleated giant cells. Intense expression of FGF-b was statistically associated with younger cats (P < 0.01) and with tumors with nodular growth patterns (P = 0.02). In addition, sarcomas negative for p53 protein expressed FGF-b more frequently than did p53-positive tumors (P = 0.04). The frequency of FGF-b immunostaining was significantly higher in sarcomas with intense expression of TGF-alpha (P = 0.05). Immunohistochemical detection of p53 protein, FGF-b, and TGF-alpha suggests that these growth-regulating proteins may play different roles in the development of sarcomas associated with vaccine sites.

Topics: Animals; Cat Diseases; Cats; Fibroblast Growth Factor 2; Immunohistochemistry; Sarcoma; Transforming Growth Factor alpha; Tumor Suppressor Protein p53; Vaccination

The aim of this review was to describe expression of epithelial growth factor receptor (EGFR) and of its ligands in a panel of tumours (which are not specified elsewhere in this special issue of Bulletin du Cancer): squamous cell carcinomas, adenocarcinomas, sarcomas, brain and germ line tumours. The role of EGFR and its ligands in the carcinogenesis and the progression of these tumours, as well as the relevance of targeting EGFR.

Topics: Adenocarcinoma; Carcinoma, Squamous Cell; ErbB Receptors; Female; Humans; Male; Neoplasm Proteins; Neoplasms; Sarcoma; Transforming Growth Factor alpha

Human epithelioid sarcoma (ES) is an extremely aggressive soft tissue tumour of unknown histogenesis. Although growth factor-dependent signalling cascades significantly affect the biological behaviour of malignant tumours, little is known so far about their role in human ES. The present investigation, therefore, analyses the coexpression and function of different growth factors and their receptors in the human ES cell line GRU-1 and its clonal subpopulations (GRU-1A, GRU-1B and GRU-1C). As shown by Northern blot, flow cytometry, immunocytochemistry and MTT assay, all ES cell lines expressed transforming growth factor (TGF)-alpha and the epidermal growth factor receptor (EGF-R). Although no response to exogenous TGF-alpha was observed, antagonistic anti-EGF-R antibodies (at 20 microg/ml) induced significant (P<0.05) growth inhibition in all cell lines. All cell lines showed coexpression of platelet-derived growth factor (PDGF)-A and the corresponding receptors. Neutralisation of ES-derived PDGF by anti-hPDGF antibodies resulted in significant (P<0.05) growth inhibition of all clonal subpopulations. Although all cell lines expressed TGF-beta(1) as well as TGF-beta type I and type II receptors (TGF-BI-R and TGF-BII-R), growth inhibition (P<0.05) by exogenous TGF-beta(1) was achieved in the clonal subpopulations only and not in the parental cell line. No ES cell line expressed acidic fibroblast growth factor (FGF) but stimulation of FGF type 3 and type 4 receptors (FGF-3R and FGF-4R) by exogenous acidic FGF (aFGF) resulted in a marked (P<0.05) acceleration of proliferation in all cell lines. In conclusion, our investigation suggests an intricate network of autocrine, juxtacrine and paracrine signalling between ES tumour cells and adjacent non-neoplastic stromal cells.

Topics: Blotting, Northern; Cell Communication; Cell Division; Enzyme-Linked Immunosorbent Assay; ErbB Receptors; Fibroblast Growth Factors; Flow Cytometry; Humans; Immunohistochemistry; Neoplasms, Glandular and Epithelial; Platelet-Derived Growth Factor; Receptors, Fibroblast Growth Factor; Receptors, Platelet-Derived Growth Factor; RNA, Messenger; Sarcoma; Transforming Growth Factor alpha; Transforming Growth Factor beta; Tumor Cells, Cultured

The varying tumorbiological behaviour of ovarian carcinomas probably influences operability, response to chemotherapy, being one of the most relevant prognostic factors. Because it is believed that an activation of the epidermal growth factor/transforming growth factor alpha (EGF/TGF alpha) signal pathway could be involved, we analysed the expression of epidermal growth factor receptor (EGFR) and TGF alpha with molecular-chemical, biochemical and immunohistochemical methods in 42 ovarian carcinomas, 4 ovarian metastasis, 2 other malignant ovarian tumours, and in 25 nonmalignant tissues (ovary, myometrium). No major rearrangements or amplification of the EGFR or TGF alpha genes were found. In non-malignant tissues no strong EGFR or TGF alpha signals were detected. TGF alpha is mainly produced by the tumour cells as shown by immunohistochemistry. Four different high molecular weight forms (20-48 kD) were detected in malignant tissues by western blot analysis.

Topics: Blotting, Northern; Blotting, Southern; Blotting, Western; Carcinoma; DNA, Neoplasm; ErbB Receptors; Female; Humans; Immunohistochemistry; Ovarian Neoplasms; Placenta; Pregnancy; RNA, Messenger; Sarcoma; Teratoma; Transforming Growth Factor alpha