A Multiplexed Gene Expression Approach to Evaluating Metastasis
The nCounter PanCancer Progression Panel is a new panel developed to assist researchers with the challenge of assessing cancer progression. The panel has 770 genes from four major biological processes that contribute to increased tumor growth and invasiveness, including angiogenesis, the epithelial-to-mesenchymal transition, extracellular matrix remodeling, and metastasis.
- Investigate the state of cancer progression
- Measure treatment effects on angiogenesis
- Assess the extracellular matrix and remodeling mechanisms
- Detect key genes that mark the epithelial-to-mesenchymal transition
- Quantify the expression of metastatic growth and suppressor genes
Distribution of Genes in the PanCancer Progression Panel
770 genes including angiogenesis, extracellular matrix, epithelial-to-mesenchymal transition, and metastasis. Components of each feature are highlighted.
Key Features and Genes Involved in Cancer Progression
The processes of the primary tumor that lead to changes in microenvironment, tumor growth, and cell dissemination are shown, such as hypoxic conditions, metabolism changes, and ECM remodeling. After tumor cells undergo EMT and invade a new site, additional metastatic hurdles need to be overcome, including enabling angiogenesis and avoiding tumor dormancy. The genes listed are important players in each of the major processes and potential therapy targets.
Angiogenesis is the biological process of generating new blood vessels from pre-existing vasculature. In the disease state, angiogenesis is induced quite early in cancer development, a process often referred to as turning on an “angiogenic switch”1. Angiogenesis is of particular interest in cancer progression considering that distant tumors cannot grow more than 2-3 cubic mm without vasculature2.
The extracellular matrix (ECM) is an assembly of proteins and sugars that surrounds cells in solid tissues, primarily providing mechanical structure to cells. The ECM must be remodeled in order to accommodate tumor growth. Tumor cells rely on the MMP and LOX gene families to change the surrounding ECM environment3. Several of these remodeling genes have further roles in progression, acting as transcription factors in metastatic growth4.
The epithelial-mesenchymal transition (EMT) is a process that cancer cells undergo which promotes metastatic progression. Epithelial cells are defined by their ability to laterally tether to each other in sheets using intercellular junctions5, whereas mesenchymal cells are more elongated for motility and rely on focal adhesions for attachment6. The epithelial-mesenchymal transition (EMT) is a dynamic spectrum between these two states that can be reversible depending upon intra- and extra- cellular factors7.
Metastasis is a collection of cellular processes encompassing cell migration from the primary tumor to successful development of a distant tumor. While all of the general processes noted above occur in secondary tumors, several of the processes that are not included in the major three themes have been grouped into the term ‘metastasis’. This term includes general cell growth signaling pathways, hypoxia response, and metabolic changes. Additionally, there are a set of metastasis suppressor genes that each potential new tumor site must avoid8.
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