Project description:This SuperSeries is composed of the following subset Series:; GSE9712: Detection of genes differentially expressed in radioresistant tumors; GSE9713: Detection of genes differentially expressed in radioresistant and radiosensitive tumors before and after irradiation; GSE9714: Interferon response of radioresistant and radiosensitive human head&neck tumor cell lines Experiment Overall Design: Refer to individual Series
Project description:Prostate cancer cell lines DU145 and LNCaP were purchased from the American Type Culture Collection. Radioresistant (RR) sublines were generated form these original parental radiosensitive (RS) cell lines. Gene expression profiles of radiosensitive (RS) and radioresistant (RR) prostate cancer cell lines were measured.
Project description:Prostate cancer cell lines DU145 and LNCaP were purchased from the American Type Culture Collection. Radioresistant (RR) sublines were generated form these original parental radiosensitive (RS) cell lines. aCGH profiles of radiosensitive (RS) and radioresistant (RR) prostate cancer cell lines were measured and compared to normal DNA.
Project description:Nu61, a radiation-resistant human tumor xenograft, was selected from a parental radiosensitive tumor SCC-61 by eight serial cycles of passage in athymic nude mice and in vivo irradiation. Obtained tumors were profiled using Affymetrix U133A arrays. Most abundant gene pattern associated with radioresistant phenotype was presented by IFN-inducible, Stat1-dependent pathway Keywords: Pair-wise comparison of radiosensitive vs radioresistant tumors; time course of irradation response
Project description:Radioresistance is a major hurdle in the treatment of head and neck squamous cell carcinoma (HNSCC). Here we report a novel role for statin-based treatment of HNSCCs as an actionable and safe adjuvant to radiotherapy. Proteomic profiling and comparison of radiosensitive and radioresistant HNSCCs revealed differential regulation of the mevalonate biosynthetic pathway. Consistent with this finding, inhibition of the mevalonate pathway by pitavastatin (and other related statins) sensitized SQ20B cells to ionizing radiation (IR) and reduced their clonogenic potential. In an effort to uncover the mechanism behind this statin-mediated sensitization, we analyzed prenylation of several important cellular targets upon combined IR-statin treatment. Overall, this study reinforces the view that the mevalonate pathway is a promsing novel therapeutic target in radioresistant HSNCCs.
Project description:Head and neck squamous cell carcinoma (HNSCC) patients have a very short survival. To improve patient survival, there is an emerging need for a better understanding of the obstacles of ionizing irradiation (IR), besides surgery, currently the best treatment option for HNSCC. A confounding factor is the immune suppressive tumor microenvironment (IS-TME) which is orchestrated by tenascin-C (TNC), a highly abundant extracellular matrix (ECM) molecule, getting upregulated by IR. Here, we investigated the roles of TNC on IR-induced tumor regression in a murine oral squamous cell carcinoma (OSCC) model expressing or lacking TNC. While tumors in a TNC-expressing host were radiosensitive, tumors in the TNC genetically-depleted mice were radioresistant pointing at a so far underexplored function of TNC in promoting anti-tumor defense. Upon IR, fibroblast reticular cells (FRCs), a known source of TNC, were more numerous and promoted the IS-TME only in the TNC-expressing tumors. We applied IR to FRCs isolated from lymph nodes and observed that whereas TNC-expressing FRCs were radiosensitive, the TNC-depleted FRCs were radioresistant mimicking the tumor phenotype. Irradiation enhanced the crosstalk of TNC-expressing FRCs with the OSCC causing enhanced tumor cell death but also tumor-promoting plasticity in the survivors as well as induction of Rad51, indicative of enhanced double strand DNA break repair and radioresistance. On the other hand, IR also increased TNC and CCL21 expression in the cocultured FRCs, enforcing an IS-TME. These results demonstrate that TNC determines the FRC tumor promoting phenotype counteracting IR-induced tumor regression, which is relevant in human cancer as a high FRC signature in conjunction with high TNC levels correlates with shorter survival in the irradiated HNSCC patients. We propose that tumor FRCs highly expressing TNC may be an excellent novel target to improve radiotherapy-induced tumor eradication.
Project description:Nu61, a radiation-resistant human tumor xenograft, was selected from a parental radiosensitive tumor SCC-61 by eight serial cycles of passage in athymic nude mice and in vivo irradiation. Obtained tumors were profiled using Affymetrix U133A arrays. Most abundant gene pattern associated with radioresistant phenotype was presented by IFN-inducible, Stat1-dependent pathway Keywords: Pair-wise comparison of radiosensitive vs radioresistant tumors
Project description:Head and Neck Squamous Cell Carcinoma (HNSCC) is a common cause of cancer death. Despite enormous technical advances in surgery and radiotherapy in the recent decade, survival of HNSCC patients has not markedly improved, with only 30% of patients diagnosed with advanced HNSCC that will survive for 5 years. This highlights the need to look into molecular processes leading to mechanisms of HNSCC radioresistance in HNSCC and identify novel radiosensitizers. A growing body of evidence suggests that long non-coding RNAs (lncRNA) containing small open reading frames (sORFs) produce biologically active micropeptides. We performed ribosome profilming of radiosensitive and radioresistant HNSCC cells to identify the lncRNA-encoded micropeptides differentially expressed in radioresistance cellls.
Project description:Nu61, a radiation-resistant human tumor xenograft, was selected from a parental radiosensitive tumor SCC-61 by eight serial cycles of passage in athymic nude mice and in vivo irradiation. Obtained tumors xenografts were profiled in two independent experiments using Affymetrix U133A arrays. Most abundant gene pattern associated with radioresistant phenotype was presented by IFN-inducible, Stat1-dependent pathway. In these experiments we detected genes responding to IFN alpha, beta and gamma in nu61 and SCC61 Keywords: Pair-wise comparison of un-treated and treated tumor cell lines