Cancer Cancers arise when critical genes are mutated, causing unregulated proliferation of cells. These rapidly dividing cells pile up on top of each other to form a tumor. When cells detach from the tumor and invade surrounding tissues, the tumor is malignant and may form secondary tumors at other locations in a process called metastasis. A tumor whose cells do not invade surrounding tissues is benign.
Tumor – is a condition where there is abnormal cellular growth thus forming a lesion or in most cases, a lump in some part of your body. Benign tumor – grows in confined area Malignant tumor – capable of invading surrounding tissues Cancer – degenerative disease with a cellular condition where there is uncontrolled growing mass of cells capable of invading neighboring tissues and spreading via body fluids to other parts of the body.
Named for site of origin Carcinomas – epithelial cells; cover external & internal body surfaces (90%) Sarcomas – supporting tissue; bone, cartilage, fat, connective tissue, pancreas, Liver. Lymphoma & leukemias – blood & lymphatic tissue (leukemia reserved for cancers that reside in bloodstream not as solid tissue)
Comparison of Normal and Tumor Growth in the Epithelium of the Skin
Growth properties of normal and cancerous cells
Hematoxylin (nucleus) and Eosin (cytoplasm) stain
Normal cells vs. Cancer cells Normal cell proliferationCancer cell proliferation Anchorage dependentAnchorage independent Density-dependent inhibitionCan grow on top of one another Limited number of cell divisions Immortal Telomere shorteningTelomere maintenance Proliferation dependent upon extracellular signals Constant signal to divide Checkpoints activated at appropriate times Loss of checkpoint Apoptosis functionalApoptosis inhibited independent
Basic Properties of a Cancer Cell –In culture, normal cells can be transformed by chemicals or viruses. –Different types of cancer cells share a number of similarities: Aberrant chromosome numbers (aneuploidy) High metabolic requirements Unregulated growth Synthesis of unusual cell surface proteins
Invasion Metastasis Why? How? Basal lamina Matrix Stages in the Process of Invasion and Metastasis
Loss of cell surface proteins involve in cell-cell adhesion E-cadherin Increased Motility signaling molecules, chemoattractants, protease activator (plasminogen plasmin) Basal lamina
Some cells are more capable than others 99%
Some preferential sites blood flow patterns: capillaries (5-10 um of diameter vs 20 x 25 um) “seed and soil” Surrounding environment
pAPC controls proliferation and differentiation of cells. pAPC mutations are associated with adenomatous polyposis coli, which often leads to colorectal cancer. pAPC regulates the renewal of cells in the epithelium of the large intestine. Loss of pAPC function results in the formation of polyps. pAPC binds to catenin, which binds to transcription factors. Cells with mutations in pAPC lose their ability to control catenin levels. Familial adenomatous polyposis (FAP):rare autosomal dominant dissease.
Interaction of Ti plasmid DNA with the plant genome Bacteria genetically engineer plants to control their differentiation (tumorigenic) and production of opines that can only be catabolized by the infecting Agrobacterium strain. HOOC-C-NH-C-COOH R1 R2 HH
T-DNA transfer, single strand invasion
Transfer of T-DNA resembles bacterial conjugation T-DNA is generated when a nick at the right boundary creates a primer for synthesis of a new DNA strand. The preexisting single-strand that is displaced by the new synthesis is transferred to the plant cell nucleus. Transfer is terminated when DNA synthesis reaches a nick at the left boundary. The T-DNA is transferred as a complex of single-stranded DNA with the VirE2 single-strand binding protein. The single stranded T-DNA is converted into double-stranded DNA and integrated into the plant genome. The mechanism of integration is not known. T-DNA can be used to transfer genes into a plant nucleus (transformation).