Invade and Metastasize - Metastasis causes 90% of cancer deaths
90% of cancer deaths have been attributed to the ability of cancer cells to invade and metastasize. Cancer cells migrate and invade through different tissue types enabling them to intravasate/extravasate blood and lymphatic vessels and produce the metastases. Cancer cells are able to modify their migration mechanisms in different conditions using individual and collective cell-migration strategies. As such, cancer therapeutics designed to target adhesion receptors or proteases have not proven to be effective in slowing tumour progression in clinical trials. Improved understanding of cellular and molecular basis of tumor migration and invasion strategies will improve therapeutic outcomes.
Studying cancer cell migration and invasion using techniques that are kinetic, quantitative, reproducible, and efficient, will enable collection of highly reproducible data over time ranges spanning from minutes to days.
We at In Vitro Technologies are committed to your groundbreaking cancer research to understand how cancer cells ‘invade and metastasize’ and identify improved therapeutic strategies. So we have brought together a range of quality resources to help you explore this hallmark. With our expert support, the solutions we offer guarantee high quality, reproducible results, allowing you to accelerate cancer discoveries.
Epithelial to mesenchymal transition in cancer cells
Epithelial to mesenchymal transition (EMT) occurs as a normal physiological function during development (Type 1 EMT) and wound healing (Type 2 EMT). However, Type 3 EMT is associated with cancer progression and metastasis. Tumor cells that leave the primary tumor to develop a new tumor at a distant site undergo a metastatic cascade. This dissemination on cancer cells involving circulating tumor cells (CTCs) is an essential step for metastasis. EMT transition is accompanied by loss of cell polarity and cell-cell contact, as well as downregulation of epithelial genes together with upregulation of mesenchymal genes.
Different inducers of EMT were identified. These include transforming growth factor-beta (TGF-β), tumour necrosis factor-alpha (TNF-α) and Notch, Hedgehog and Wnt molecular pathways. All these stimuli induce EMT by upregulating trascription factors, such as Snail, Twist and Zeb1, which promote cell polarity loss by destroying tight junctions and degrading adhesion molecules, such as E-cadherin (Ricciardi et al 2015).
Increasing evidence suggests that numerous signaling pathways interact to induce or inhibit EMT. TGF-β is an established inducer of EMT and R&D Systems recently presented a review that TGF-beta-Induced Epithelial-to-Mesenchymal Transition Promotes Breast Cancer Progression. Read more
Enable the real-time monitoring of the changing status of cells from epithelial to mesenchymal
Epithelial-mesenchymal transition (EMT) and its reverse, mesenchymal-epithelial transition (MET) are developmental programs which have been shown to play critical roles in promoting metastasis and invasion as well as contribute to drug resistance in carcinoma. ATCC has employed CRISPR/Cas9 gene editing to develop its first reporter line designed to enable the real-time monitoring of the changing status of cells from epithelial to mesenchymal.
Luminescent reporter assays illuminate EMT induced cell signalling.
A recent Oncogene paper highlighted the importance of Topoisomerase Iiα induced EMT in metastatic colon cancer.
Bowel cancers, like colon cancer are the most commonly reported cancer in New Zealand, with around 3000 new cases and 1200 deaths each year. New Zealand has one of the highest bowel cancer rates in the world, and Bowel cancer is the second highest cause of cancer death in New Zealand (NZ Ministry of Health)
The researchers used a Promega reporter assay with the ONE-Glo™ Luciferase Assay System to measure activation of the wnt pathway. They cultured wild type and mutant tumour microspheroids and monitored their viability with the CellTiter-Glo® 3D Cell Viability Assay.
If you are investigating the metastatic Hallmarks of Cancer then Promega reporter vectors and the ONE-Glo Luciferase Assay system provides a highly sensitive, robust, homogeneous assay for detection of firefly luciferase reporter gene expression in mammalian cells.
Suitable for high throughput screening formats, the Promega ONE-Glo system is stable at room temperature, with a brighter, longer-lasting signal and easy to use format to improve assay precision.
