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View the Table of Contents for the December 1 issue of Cancer Research.
Roepman et al. Page 11110
Spread of cancer and development of solid metastases at distant sites is the main cause of cancer-related deaths. In head and neck squamous cell carcinoma (HNSCC), metastasis nearly always occurs in local lymph nodes first, before distant metastasis develops. Roepman et al. investigated gene expression patterns in HNSCC lymph node metastases using DNA microarrays. Only a single gene, metastasis-associated gene 1 (MTA1), was found to show consistently changed expression between a large number of matched primary tumor-lymph node metastasis pairs. The maintained expression pattern includes the predictive signature for HNSCC lymph node metastasis. These results underscore the importance of the primary tumor gene expression profile for development and treatment of metastasis. The findings also agree with the concept that disseminated cancer cells alter the surrounding tissue into a metastatic environment that resembles the primary tumor microenvironment.
Enomoto et al. Page 11131
The vast majority of cancer cell lines will not generate liver metastases in animals when administered as single-cell suspensions. Enomoto et al. have improved upon existing animal models of liver metastases by encapsulating human pancreatic cancer cells in 300 µm microcapsules (MCs), mimicking micrometastatic foci and engineered by conventional co-axial airflow methods. They then transplanted the cells to the liver of rats via portal vein injection. Liver metastases were successfully obtained, though administration of single cells did not lead to liver metastases. This cancer MC method, enhancing the effect of mechanical entrapment to target organs, may be a useful tool for producing liver metastases in animal models, particularly when cell lines fail to produce tumors using conventional approaches.
Bouvet et al. Page 11293
The role of host cells in tumor progression and metastasis is critical, yet still poorly defined mechanistically. Injection of tumor cells into the spleen has long been used as an effective method of inducing liver metastases, however, the role of host spleen cells in this model is not well understood. Bouvet et al. report that after splenic injection of tumor cells expressing red fluorescent protein (RFP), host splenocytes expressing green fluorescent protein (GFP), co-migrated with the tumor cells to the liver and facilitated metastatic colony formation. The results suggest a novel tumor-host interaction that enables efficient formation of liver metastasis via cooperation with spleen-derived host cells.
Puttini et al. Page 11314
Resistance to imatinib represents an important scientific and clinical issue in chronic myeloid leukemia (CML). Puttini et al. studied the effects of the novel inhibitor SKI-606 on various models of resistance to imatinib. In vitro and in vivo studies demonstrated that SKI-606 is 50-100 fold more potent than imatinib. It is active in models of imatinib resistance including CML cells with Bcr-Abl point mutations or in cells which overexpress the oncogene. SKI-606 binds to an intermediate conformation of Bcr-Abl at a site different than imatinib. Unlike both imatinib and dasatinib, SKI-606 does not significantly inhibit PDGFR or KIT activity and, as such, is a promising molecule to expand into clinical trials.
Maher et al. Page 11502
Primary and secondary glioblastomas (GBM) evolve from distinct clinical histories to an indistinguishable pathobiological and clinical endpoint. Using high-resolution, whole-genome copy number analysis of clinically annotated samples, Maher et al. identified over 100 recurrent amplification and deletions, most of which were not shared between the two clinical entities, attesting to their underlying molecular differences. Accordingly, a novel classification methodology; genomic nonnegative matrix factorization, defined three distinct genomic classes for GBM corresponding to the known primary GBM subtype, but further stratifying the secondary GBM subtypes into two subgroups. The discovery of a large number of novel loci and these radically distinct subclasses should impact on the design of treatment strategies for these very different GBM subclasses.