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View the Table of Contents for the November 1 issue of Cancer Research.
Hayashita et al. Page 9628
Hayashita et al. report evidence that a polycistronic miRNA cluster, miR-17-92, is frequently and markedly overexpressed with occasional gene amplification, especially in the most aggressive form of lung cancer, SCLC. Introduction of miR-17-92, but not C13orf25-containing miR-17-92, was found to enhance lung cancer cell growth. Involvement of miR-17-92 in lymphoma and its cross talk with c-myc was reported recently, and this independent study further suggests that miR-17-92 may contribute to the development of lung cancers, and possibly of other solid tumors.
Wong et al. Page 9789
Although tumors metastasize to draining lymph nodes via lymphatic vessels, the role of intratumoral lymphatics in mediating the process has remained controversial. Using a combination of VEGF-C siRNAs and VEGFR-3 soluble receptor, Wong et al. show that intratumoral lymphatics are unnecessary for lymph node metastasis in an orthotopic prostate cancer model. TRAMP spontaneous prostate tumors also metastasized to lymph nodes in the absence of intratumoral lymphangiogenesis. In both cases, peritumoral lymphatics at the tumor-stromal junction were likely sufficient for mediating lymph node spread. These findings emphasize the importance of targeting peritumoral lymphatics, if lymph node metastasis is to be prevented.
Röhn et al. Page 10068
The limited availability of MHC class II-restricted tumor antigens is viewed as an obstacle in immunotherapy of cancer. By combining exposure of tumor cells to human dendritic cells (DC) and HPLC/ion trap mass spectrometry, Röhn et al. identify a novel MHC II peptide epitope derived from the tumor marker melanotransferrin (MTf). The MTf peptide is not only presented by DC but also by MHC II-positive melanoma cells and stimulated T cells from melanoma patients and healthy individuals. Thus, this approach proves suitable to identify epitopes of tumor-specific markers and may aid in improving future vaccines against cancer.
Dubé et al. Page 10088
PTP1B is an important target for the treatment of diabetes and obesity, as it negatively regulates insulin signaling. Based on its substrates and expression in human tumors and cell lines, PTP1B inhibition could potentially enhance oncogenic signaling, but PTP1B-/- mice do not develop spontaneous tumors. Here, Dubé et al. demonstrate that PTP1B is an important determinant of B-cell development and p53-dependent tumorigenesis as p53/PTP1B double null mice exhibit decreased survival rate and a higher proportion of B-cell lymphomas compared to p53-/- littermates. Importantly, the mean time of tumor development and tumor spectrum are unchanged in p53-/-PTP1B+/- mice, suggesting that pharmacological inhibition of PTP1B would not lead to detrimental effects.
Howe et al. Page 10113
Cox-2 is overexpressed in ~40% of human breast cancers and, in particular, correlates with HER2/neu overexpression. To definitively interrogate the role of Cox-2 in mammary neoplasia, Howe et al. cross Cox-2 knockout mice with a HER2/neu transgenic strain. Mammary tumor multiplicity and size were significantly decreased in Cox-2-deficient animals relative to Cox-2 wild-type controls. Additionally, strikingly diminished vascularization was observed both in dysplastic and normal-appearing regions of Cox-2 null mammary glands. These data provide the first genetic evidence that Cox-2 contributes to HER2/neu-induced mammary tumorigenesis, and suggest an unanticipated role for Cox-2 in vascularization of normal mammary gland.