Caroline Speed; Week 7 MED1011; Biochemistry
Cell divisions are not continous, controlled by external stimuli, nutrient availability. Extracellular signals cause intracellular biochemical response (cell cycle entry, arrest in G1/G0 phase). There are over 200 growth factors. Growth factors regulate cell cycle progression, cell survival, migration and death. Withdrawal of growth factors favours apoptosis, presence inhibits (EPO, GM-CSF). Tumours can produce growth factors that stimulate tumour growth in an autocrine manner. Proliferation of cells may be limited by maturation into resting or quiescent state, post mitotic differentiation, apoptosis (disrupted in cancer cells). Cancer cells ignore signals to enter G0 and continue proliferating. Cancer cells fail to terminally differentiate. Cancer requires 4 to 6 mutations to reach the tumour state, can take decades for a single mutant to proliferate to a palpable tumour. Tumorigenesis proceeds by clonal expansion- increasingly abnormal cells outgrow neighbours.
Cancer cells do not stop dividing when they contact a neighbouring cell, do not require attachment to physical substrate to grow, have reduced requirement for growth factors to grow and are resistant to growth inhibitory signals. Cancer cells are immortal and often have chromosomal aberrations, also has telomerase for immortality. Usually, tissue mass is a balance between proliferation and apoptosis.