Cellular changes towards cancerous development and spread as described by Hanahan and Weinberg [22].
(1) Self-sufficiency in growth signals—changing the intra- or extracellular response to existing growth factors, increasing the production of growth factor via self-production or by stimulating neighboring cells.
(2) Insensitivity to antigrowth signals—changing of growth factor receptors or signaling pathways.
(3) Antiapoptosis—changing the intra- or extracellular sensors that induce apoptosis such as tumor suppressor protein 53 (p53).
(4) Sustained angiogenesis—production of vascular endothelial growth factor (VEGF) and other factors.
(5) Unrestrained replicative potential—production of telomerases ensuring that the telomeres on the chromosomes avoid normal progressive shortening during abnormally increased cell cycles.
(6) Tissue invasion and metastasis—reducing adhesion to other cells and the extracellular matrix by decreasing CAMs (adhesion molecules), calcium dependent cadherin families, especially E-cadherin and integrins. Increasing protease productions from the tumor, stromal or immunological cells enables tumor spread. The cells have to adhere to the new tissue by expressing adhesive molecules.
