Identification of potential lung cancer biomarkers using an in vitro carcinogenesis model

Abstract

Lung cancer is one of the deadliest and commonly diagnosed neoplasms. Early diagnosis of this disease is critical for improving clinical outcome and prognosis. Because the early stages of lung cancer often produce no symptoms, it is necessary to identify biomarkers for early detection, prognostic evaluation, and recurrence monitoring of the cancer. To identify potential lung cancer biomarkers, we analyzed the differential protein secretion from transformed bronchial epithelial cells (1198 and 1170-I) as compared to immortalized normal bronchial epithelial cells (BEAS-2B) and non-transformed cells (1799) all of which are derived from BEAS-2B and represent multistage bronchial epithelial carcinogenesis. The proteins recovered from the conditioned media of the cells were separated on two-dimensional gels. There was little difference between the secretome of the BEAS-2B and 1799 cells, whereas the patterns between the transformed 1198 and 1170-I cells and non-transformed 1799 cells were significantly different. Using mass spectrometry and database search, we identified 20 proteins including protein gene product 9.5 (PGP9.5), translationally controlled tumor protein (TCTP), tissue inhibitors of metalloproteinases-2 (TIMP-2), and triosephosphate isomerase (TPI), that were either increased or decreased simultaneously in conditioned media of both 1198 and 1170-I cells. Furthermore, levels of PGP9.5, TCTP, TIMP-2, and TPI were significantly increased not only in the conditioned media of both transformed cell lines when compared to those of BEAS-2B and 1799 cells, but also in plasmas and tissues from lung cancer patients when compared to those in normal controls. We suggest the PGP9.5, TCTP, TIMP-2, and TPI as promising candidates for lung cancer serum biomarkers.

Targeted Efficacy of Dihydroartemisinin for Translationally Controlled Protein Expression in a Lung Cancer Model

“…The higher concentration of DHA was not suitable for the cell secretion study since it could induce cell apoptosis. Kim et al analyzed the secretome of transformed bronchial epithelial cells (1198 and 1170-I), the parental immortalized normal cells (BEAS-2B) and non-transformed cells (1799) (Kim et al, 2008). The levels of TCTP were significantly increased in the conditioned media of both transformed cell lines when compared with those of BEAS-2B and 1799 cells.…”

Roles of the translationally controlled tumour protein (TCTP) and the double-stranded RNA-dependent protein kinase, PKR, in cellular stress responses

“…TCTP protein levels are upregulated in cancer cells and in human tumours (Tuynder et al, 2004;Kim et al, 2008a;Ma et al, 2009;Slaby et al, 2009). Downregulation of TCTP has been implicated in biological models of tumour reversion (Tuynder et al, 2002(Tuynder et al, , 2004, and the protein is the target of various anticancer drugs (Tuynder et al, 2004;Efferth, 2005), of which one has entered a phase-I/II clinical trial (Telerman and Amson, 2009).…”

“…Downregulation of TCTP has been implicated in biological models of tumour reversion (Tuynder et al, 2002(Tuynder et al, , 2004, and the protein is the target of various anticancer drugs (Tuynder et al, 2004;Efferth, 2005), of which one has entered a phase-I/II clinical trial (Telerman and Amson, 2009). TCTP has been proposed as a potential biomarker for lung cancer (Kim et al, 2008a) and for progression of tumorous mycetoma (van de Sande et al, 2006). Gene-knockout studies have established the importance of TCTP in developmental regulation.…”

microRNA-145 promotes differentiation in human urothelial carcinoma through down-regulation of syndecan-1

“…UCHL-1 is overexpressed in pancreatic endocrine tumors, as well as in colorectal and lung cancers. This enzyme is a neuroendocrine marker that recognizes and hydrolyzes a peptide bond at the C-terminus of ubiquitin, and remodels synapses by controlling ubiquitin homeostasis [31][32][33]. In the current study, miR-145 provided to suppress cell proliferation and reverse urothelial carcinomas to the pluripotent cells with stem cell features through induction of senescence, then prompted differentiation to multiple lineages such as squamous, glandular and neuroendocrine cells.…”