ABSTRACT
BACKGROUND: The development and progression of cancer depend on its genetic characteristics as well as on the interactions with its microenvironment. Understanding these interactions may contribute to diagnostic and prognostic evaluations and to the development of new cancer therapies. Aiming to investigate potential mechanisms by which the tumor microenvironment might contribute to a cancer phenotype, we evaluated soluble paracrine factors produced by stromal and neoplastic cells which may influence proliferation and gene and protein expression. METHODS: The study was carried out on the epithelial cancer cell line (Hep-2) and fibroblasts isolated from a primary oral cancer. We combined a conditioned-medium technique with subtraction hybridization approach, quantitative PCR and proteomics, in order to evaluate gene and protein expression influenced by soluble paracrine factors produced by stromal and neoplastic cells. RESULTS: We observed that conditioned medium from fibroblast cultures (FCM) inhibited proliferation and induced apoptosis in Hep-2 cells. In neoplastic cells, 41 genes and 5 proteins exhibited changes in expression levels in response to FCM and, in fibroblasts, 17 genes and 2 proteins showed down-regulation in response to conditioned medium from Hep-2 cells (HCM). Nine genes were selected and the expression results of 6 down-regulated genes (ARID4A, CALR, GNB2L1, RNF10, SQSTM1, USP9X) were validated by real time PCR. CONCLUSIONS: A significant and common denominator in the results was the potential induction of signaling changes associated with immune or inflammatory response in the absence of a specific protein.
Subject(s)
Gene Expression Regulation, Neoplastic , Mouth Neoplasms/metabolism , Proteome/metabolism , Annexin A5/metabolism , Apoptosis , Cell Proliferation , Down-Regulation , Electrophoresis, Gel, Two-Dimensional , Fibroblasts/metabolism , Genomics , Hep G2 Cells , Humans , Keratins/metabolism , Mouth Neoplasms/genetics , Nucleic Acid Hybridization , Spectrometry, Mass, Matrix-Assisted Laser Desorption-Ionization , Stromal Cells/metabolism , Vimentin/metabolismABSTRACT
AIMS: Annexin A1 (ANXA1) is a soluble cytoplasmic protein, moving to membranes when calcium levels are elevated. ANXA1 has also been shown to move to the nucleus or outside the cells, depending on tyrosine-kinase signalling, thus interfering in cytoskeletal organization and cell differentiation, mostly in inflammatory and neoplastic processes. The aim was to investigate subcellular patterns of immunohistochemical expression of ANXA1 in neoplastic and non-neoplastic samples from patients with laryngeal squamous cell carcinomas (LSCC), to elucidate the role of ANXA1 in laryngeal carcinogenesis. METHODS AND RESULTS: Serial analysis of gene expression experiments detected reduced expression of ANXA1 gene in LSCC compared with the corresponding non-neoplastic margins. Quantitative polymerase chain reaction confirmed ANXA1 low expression in 15 LSCC and eight matched normal samples. Thus, we investigated subcellular patterns of immunohistochemical expression of ANXA1 in 241 paraffin-embedded samples from 95 patients with LSCC. The results showed ANXA1 down-regulation in dysplastic, tumourous and metastatic lesions and provided evidence for the progressive migration of ANXA1 from the nucleus towards the membrane during laryngeal tumorigenesis. CONCLUSIONS: ANXA1 dysregulation was observed early in laryngeal carcinogenesis, in intra-epithelial neoplasms; it was not found related to prognostic parameters, such as nodal metastases.
Subject(s)
Annexin A1/metabolism , Carcinoma, Squamous Cell/metabolism , Laryngeal Neoplasms/metabolism , Adult , Aged , Aged, 80 and over , Annexin A1/analysis , Annexin A1/genetics , Blotting, Western , Carcinoma, Squamous Cell/pathology , Female , Gene Expression , Humans , Immunohistochemistry , Laryngeal Neoplasms/pathology , Male , Middle AgedABSTRACT
Papillary carcinoma, the commonest thyroid malignancy, has a good prognosis and low incidence of distant metastases. Brain metastasis is extremely rare with a frequency of about 1% in reported series. In this paper we present the clinical details of one case of histologically proven brain metastasis from papillary thyroid cancer, first presented with neurological symptoms, initially treated with excisional biopsy and radiotherapy in other hospital, without clinical response. The patient was then referred to our service, where he underwent a total thyroidectomy and modified radical neck dissection, with the aim of posterior radioactive iodine treatment for the brain lesion. Unfortunately, he died of neurological complications, two months after the neck treatment. Also presented is a review of the literature of this unusual clinical presentation.
