Determination of the Migration Potential in Breast and Lung Cancer Cells in presence of antimigratory therapeutic agent. Marco Brudik and Paloma Aranzazu Godinez Melgoza
Medical and Pharmaceutical Biotechnology Program, University of Applied Sciences IMC FH Krems.
Abstract. The new trends on research points to study the process of tomour-cell invasion and metastasis for developing and testing of anti-migratory agents. The present study develops a quantitative determination of the cancer cell’s migratory potential by Cell transendothelial migration assay. The cancer cell’s migratory potential may be affected by exposure to antimigratory agents such as Gefitinib. The Gefitinib inhibits the cellular progression and migration by blocking the EGF receptors. Our studies reveled the effect on the migration rate in breast and lung cancer with exposure to Gefitinib, consequently the migration rate decrease 20%.
Cancer is a major health problem for humankind, and the approaches to its treatment have clear limitations. Cancer kills patients essentially because of the migratory nature of its cells. Indeed, it is now well established that cell migration plays pivotal roles in cancer cell scattering, tissue invasion and metastasis, these processes are essentially responsible for the dismal prognoses of a majority of cancer patients. Thus, as an alternative to treatments designed only to kill cancer cells, researchers must today focus on developing the means to reduce or even to prevent the migration of these cells14. * Tumor-cell invasion and migration.
The process of tumour-cell invasion and metastasis is conventionally understood as the migration of individual cells that detach from the primary tumour, enter lymphatic vessels or the bloodstream and seed in distant organs. During the early stages of carcinogenesis, a disorganization of epithelial cell–cell junctional complexes may occur during the EMT process This may result in the disruption of intercellular adhesion and cell–cell dissociation, and thereby lead to the detachment of cancer cells from the tumor mass17. To migrate, the cell body must modify its shape and stiffness to interact with the surrounding tissue structures, and the protein-protein interactions and signalling events are responsible of this1. These mechanisms are integrated in the concepts of focalized adhesion dynamics2 and actomyosin polymerization and contraction 3, 4. For example the initial propulsion and elongation of the cells leads to the formation of pseudopods, which is driven by actin polymerization and assembly to filaments 4, 5. Cancer-cell migration is typically regulated by integrins, matrix-degrading enzymes, cell–cell adhesion molecules and cell–cell communication1. In vitro and in vivo observations have shown that tumour cells infiltrate neighbouring tissue matrices in diverse patterns. They can disseminate as individual cells, referred to as ‘individual cell migration’, or expand in solid cell strands, sheets, files or clusters, called ‘collective migration1. Cancer cells disseminate from the primary tumour either as individual cells, using amoeboid- or mesenchymal-type movement, or as cell sheets, strands and clusters using collective migration1. * Epithelial-mesenchymal transitions in tumor progession
The most apparent morphological change that occurs during the transition from a benign tumour to a malignant and metastatic one is that tumour cells change from a highly differentiated, epithelial morphology to a migratory and invasive phenotype8. Epithelial–mesenchymal transition (EMT) is a highly conserved and fundamental process that governs morphogenesis in multicellular organisms. During this transition, mesenchymal cells acquire a morphology that is appropriate for migration in an extracellular environment6. Loss of E-cadherin expression seems to be heavily involved in EMT, and E-cadherin is therefore emerging as one of the caretakers of the epithelial...
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