potential (immortality) Acquisition of sustained angiogenesis, allowing the tumor to grow beyond the limitations of passive nutrient diffusion. Acquisition of ability to invade neighbouring tissues, the defining property of invasive carcinoma. Acquisition of ability to seed metastases at distant sites, a late-appearing property of some malignant tumors (carcinomas or others). The completion of these multiple steps would be a very rare event without: Loss of capacity to repair genetic errors, leading to an increased mutation rate (genomic instability), thus accelerating all the other changes. These biological changes are classical in carcinomas; other malignant tumors may not need to achieve them all. For example, given that tissue invasion and displacement to distant sites are normal properties of leukocytes, these steps are not needed in the development of leukemia. Nor do the different steps necessarily represent individual mutations. For example, inactivation of a single gene, coding for the p53 protein, will cause genomic instability, evasion of apoptosis and increased angiogenesis. Further, not all the cancer cells are dividing. Rather, a subset of the cells in a tumor, called cancer stem cells, replicate themselves as they generate differentiated cells. Cancer as a defect in cell interactions Normally, once a tissue is injured or infected, damaged cells elicit inflammation by stimulating specific patterns of enzyme activity and cytokine gene expression in surrounding cells. Discrete clusters ("cytokine clusters") of molecules are secreted, which act as mediators, inducing the activity of subsequent cascades of biochemical changes. Each cytokine binds to specific receptors on various cell types, and each cell type responds in turn by altering the activity of intracellular signal transduction pathways, depending on the receptors that the cell expresses and the signaling molecules present inside the cell. Collectively, this reprogramming process induces a stepwise change in cell phenotypes, which will ultimately lead to restoration of tissue function and toward regaining essential structural integrity. A tissue can thereby heal, depending on the productive communication between the cells present at the site of damage and the immune system. One key factor in healing is the regulation of cytokine gene expression, which enables complementary groups of cells to respond to inflammatory mediators in a manner that gradually produces essential changes in tissue physiology. Cancer cells have either permanent (genetic) or reversible (epigenetic) changes to their genome, which partly inhibit their communication with surrounding cells and with the immune system. Cancer cells do not communicate with their tissue microenvironment