Part of the book: Breast Cancer
Pancreatic ductal adenocarcinoma (PDAC) is known for its early spreading of tumor cells into the liver. The aim of this study was to investigate the modulated gene expression of PDAC cells during liver colonization. To that purpose, ASML rat pancreatic cancer cells marked with enhanced green fluorescent protein were inoculated into the portal vein of isogenic BDX rats and reisolated from livers by fluorescence-activated cell sorting sorting at early (1, 3 days), intermediate (9 days), advanced (15 days), and terminal (21 days) stages of liver colonization. Reisolated ASML cells were used for total RNA isolation and subsequently their gene expression was investigated by Illumina chip array for mRNA and miRNA species, followed by Ingenuity Pathway Analysis (IPA). Following reisolation, 7–20% of genes and 10% of miRNA species were modulated significantly in expression during the early stage of liver colonization and continuously thereafter. These overall changes led to distinguish certain categories and processes participating in cancer progression. The knowledge of these alterations in gene expression will suggest targets, which could be used for new diagnostic procedures as well as for combating liver metastasis successfully.
Part of the book: Tumor Metastasis
Metastasis is the spread of tumor cells from a primary site to a secondary site within the host’s body. It is initiated by the detachment of the tumor cells from the primary tumor followed by invasion into the surrounding tissue. Thereafter the cells migrate across the endothelium and into the blood vessels (intravasation). During the intravasation the cells have to survive the sheer forces and the immune response. Upon arrival to the target organ, the cells leave the circulation and cross the endothelium to reach the host organ. Once there, the tumor cells are greeted with the organ’s local immune cells and with a hostile or inappropriate environment, where they finally have to form proliferating colonies. Metastasis is therefore far from being a straight-forward or efficient process with less than 0.1% of disseminating tumor cells (around 1 × 109 cells per day for a 1 cm size tumor) succeeding in colonizing distal organs. The identification of the involved marker during the early metastasis process will be essential for establishment of new diagnostics tools, as well as development of novel treatment strategies.
Part of the book: Cancer Metastasis
With estimated 700,000 deaths each year, colorectal carcinoma (CRC) continues to be the fourth leading cause of cancer-related deaths worldwide. Fortunately, the mortality of CRC is considered to be most avertable; hence, it is essential to develop new approaches for more accurate and early diagnosis of primary as well as metastatic CRC, including genetic and biomarker tests. In this regard, the intercellular junctions and the insulin-like growth factor (IGF) axis attract increasing attention, since they are involved in several stages of cancer and for their vital role in regulating cell survival and growth; furthermore, constituents of intercellular junctions and of the IGF axis could be used as tumor and/or metastasis markers, which are becoming the focus of increasing research activities. Our experimental results highlight the importance of gene expression changes in the tight junction proteins claudins, and in the IGF-binding proteins IGFBP3 and IGFBP7. They show additionally that claudins and IGFBPs cannot be simply defined in terms of favoring or antagonizing cancer progression but have additional properties and activities, which become apparent only in the context of liver colonization. Furthermore, their intensive modulation during the initial phase of liver colonization may suggest them as early metastasis-related markers.
Part of the book: Advances in the Molecular Understanding of Colorectal Cancer
Genetic alterations can cause cancer, including pancreatic cancer (PC) as well as certain neurodegenerative diseases. Our lab has recently identified genes that are modulated during pancreatic cancer liver metastasis, and some are known to have a role in neurobiology or neurodegenerative diseases. Autophagy or self-eating portrays the lysosomal-dependent degradation and recycling of protein aggregates and defective organisms in eukaryotic cells. Deregulation of autophagy as a cellular mechanism is common in neurodegenerative diseases as well as cancer and may represent a platform by which some genes can affect both disorders. This is exemplified for optineurin, which is an autophagy receptor that was found among genes with intensive modulation of expression in PC liver metastasis. Our results on this autophagy receptor draw the attention to the expression status of this and other autophagy genes in pancreatic cancer progression.
Part of the book: Gene Expression and Control
Pancreatic cancer is the fourth leading cause of cancer deaths, with a low 5-year survival rate of about 7% due to its highly invasive nature. Pancreatic ductal adenocarcinoma (PDAC) comprises more than 90% of all pancreatic cancer cases. At the time of detection, around 80% of cases harbor metastases due to the lack of early diagnosis. For decades, scientists have primarily focused on dissecting the origin of pancreatic cancer through genetic alterations and their contribution to diagnosis. Recently, PDAC research has turned into epigenetics to revolutionize our understanding about the silencing of critical regulatory genes. Epigenetic events can be divided mechanistically into various components, including DNA methylation, histone posttranslational modification, nucleosome remodeling, and regulation of transcription or translation by microRNA. The identified epigenetic processes in PDAC contribute to its specific epigenotype and are correlated phenotypic features. Strikingly, some of them have been suggested to have potential as cancer biomarkers, for disease monitoring, prognosis, and risk validation. As epigenetic aberrations are reversible, their correction will become as a promising therapeutic target.
Part of the book: DNA Repair