Cancer Cell Properties PDF

MODULE 46 Basic Properties of Cancer Cells: Potential for Limitless Replication After a certain number of doublings (~50+), normal cells enter senescence; however, if pRB or p53 is disabled, cells continue to multiply until they enter crisis, a state characterized by karyotypic disarray due to en...

MODULE 46 Basic Properties of Cancer Cells: Potential for Limitless Replication After a certain number of doublings (~50+), normal cells enter senescence; however, if pRB or p53 is disabled, cells continue to multiply until they enter crisis, a state characterized by karyotypic disarray due to end-to-end fusions and breakage of chromosomes. A crisis is a period in which cell growth is balanced by cell death until the cell acquires the ability to stabilize its telomeres. Cancer cells are immortal due to the maintenance of their telomeres by: - The expression of telomerase, or - Utilizing an alternative mechanism that relies on the recombination between chromosomes. Remember: senescence → pRB or p53 mutation → crisis → telomere stabilization. The Alternative Road to Immortality The Alternative Lengthening of Telomeres (ALT) pathway is a telomerase-independent pathway for telomere maintenance that is active in some human cancers. ALT involves a template-based extension of telomeres through homologous recombination. Mutations in a chromatin remodeling complex (ATRX/DAXX) and histone H3.3 correlate with features of ALT in several cancers. Basic Properties of Cancer Cells: Sustained Angiogenesis All cells need to be within 100 micrometers of a blood vessel to obtain oxygen and nutrients. Without angiogenesis, the tumor is arrested at a microscopic state (1-2 mm³); this early stage is called in situ tumor. Angiogenesis is controlled by soluble factors, their receptors on endothelial cells, and cell-matrix interactions. MODULE 46 MODULE 46 Basic Properties of Cancer Cells: Tissue Invasion and Metastasis Invasion and Metastasis : Cancer cells from the primary location spread to new locations where nutrients and space are not limited. Metastases arise as amalgams of cancer cells and normal supporting host tissue cells. Most human cancer deaths are caused by metastases. Mechanisms of Tissue Invasion and Metastasis The process involves changed interactions of the cells to their environment through: - Activation of extracellular proteases (some released by stromal and inflammatory cells). - Changes in cell-cell adhesion molecules (e.g., loss of E-cadherin function in epithelial cancers). - Changes in cell-ECM adhesion proteins (e.g., carcinoma cells switch integrin expression). Cancer versus a Successful Global Corporation Self-sufficiency in growth signals ~ Fuels its own expansion. Insensitivity to antigrowth signals ~ Counteracts growth inhibition. Evasion of apoptosis ~ Resists adverse conditions and competition. Potential for limitless replication ~ Viable without limits. Sustained angiogenesis ~ Builds its own infrastructure. Tissue invasion and metastasis ~ Acquires new resources and markets. How Are the Six Capabilities Acquired The development of cancer is a process of selection of mutations Different colors designate different mutational profiles that develop and predominate as cancer evolves under the pressure of external and internal factors How do cancer cells accumulate all "necessary" mutations? mutations are rare events because genome integrity is maintained by an array of DNA monitoring and repair enzymes; however, these enzymes may dysfunction epigenetic events also contribute to neoplastic development Putting It Together Cancer cells are characterized by limitless replication, often involving telomere maintenance. Cancers have sustained angiogenesis. Cancers eventually progress to tissue invasion and metastasis. The properties of cancer are acquired through gene expression changes based on mutations and epigenetic changes.