MICROBIO 160 1st Edition Lecture 7 Outline of Last Lecture I Evidence for Immune Reaction toTumors II How does Cancer Escape Detection III Cancer Vaccines IV Antibodies that Stimulate Cell Killing V ConjugatedAntibodies VI Antibodies that Block Receptors Outline of Current Lecture I Typical Cancer Progression II Primary and Secondary Cancer III Cancer Spread and Mortality IV How Cancer Spreads V The Metastatic Process VI Vasculogenesis vs Angiogenesis VII Tumorsneed Blood Vessels to Grow VIII Cancer Cells ProduceAngiogenesis Stimulating Molecules IX Treating Cancer by Inhibition ofAngiogenesis X TumorAngiogenesis Current Lecture Mutations can be activated by 3 gene families DNArepair genes Tumor suppressors Oncogenes Hyperplasia the enlargement of an organ or tissue caused by an increase in the reproduction rate of its cells initial stage in the development of cancer cells begin to enlarge and less organized Dysplasia abnormality of development of growth and differentiation cells grow on top of each other overlapping Carcinoma in situ cancer that has stayed in the place where it began and has not spread to neighboring tissues still localized hasn t started to invade Once you collect enough genes it leads to cancer and cancer invades transformation Primary and Secondary Cancer Metastasis is the main reason cancer can be difficult to cure Inorder to spread some cells from the primary cancer must break away travel to another part of the body and start growing there chances of survival are much better if you find it before it spreads Primary tumor the first tumor may live in the liver and can metastasize to brain second tumor where the cancer spreads Cells that metastasize will be like the original tumor Breast cancer tissues that grow in the brain will have breast tissues in the brain as well the second tumor resembles the primary Tumor causes cells to stick together cancer cells separate from the tumor then spread to other parts of the body Cancer Spread and Mortality You have a tumor hasn t started to metastasize yet small the cancer cells are sending chemical messages to different organs in the body to set up an area that it is as favorable asfavorable as possible for when it is going to metastasize Stomach cancer likes to metastasize to bone send out signals to the spine to take on characteristics that will make it more favorable when cancer lands on the bone it makes it easier to metastasize Metastasizes are so dangerous because they overwhelm the organ they can grow quickly and cause the organ to shut down Body starts off with one cell it could take years for it to be detected it eventually gets to the point where it s big enough and recognized by the immune system immune keeps it small and controls proliferation 90 of cancer deaths occur because of where cancer ends up not where it begins Most metastatic niches or landing pads allow cancerous cells to colonize a secondary organ When cancer cells travel to a vital organ they often overwhelm the cells and cause the organ to shut down Cancer Spreads Local invasion Blood When cancer cells slip out of capillary into body tissue Lymphatics Steps Involved in the Metastatic Process Cancer cells can sense from chemical messages when it has landed The ability to invade differs among cancer cells and tumor Extravasation escaping the blood vessel 1 1000survive because they are highly exposed other cells cause them to get bombarded 1 Cancer cells invade surrounding tissues and vessels Theability to invade differs among cancer cells and tumors Eachcancer has a preferred target tissue 2 Cancer cells are transported by the circulatory system to distant sites Relativelyfew cancer cells survive the voyage through the bloodstream 3 Cancer cells reinvade and grow at new location Cancer cells are able to invade because Decreased adhesiveness lose anchoring proteins Activated motility the ability to move randomly gain ability to move past macrophages Protease production squiggly lines protein fibers in tissues proteins get cut by the protease Detecting Metastasis gold standard for looking at metastasis PETscan it is a way of looking at the body and different organs In a PETscan cancer gets highlighted in pink pink resembles the abnormal lymph nodes Metabolic rate in cancer is higher than normal cells dividing and doing everything faster glucose provides the energy sucks up the most Vasculogenesis andAngiogenesis Vasculogenesis the development of new blood vessels when there are no pre existing ones Undifferentiated cells that grow blood vessels on their own Endothelial precursor cells angioblasts migrate and differentiate in response to local cues such as growth factors to form new blood vessels Has immature cells angioblasts become angiogenesis Angiogenesis the development of new blood vessels from preexisting on Mature endothelial cells lining the blood vessels start to divide in response to local cues to form new blood vessels Cells keep dividing causing them to grow out towards the cancer Has mature cells Tumors Need Blood Vessels to Grow Scientists have noticed that tumors only grow to a certain size then start to die they die from the inside out Nomatter how many nutrients they are given they still die Experiment Tumor cells were injected into anterior chamber of an eye it has no blood supply and is unable to induce blood supply Tumor cells were implanted into the iris blood supply easily induced RESULT Anterior chamber tumor did not grow signals couldn t travel to where they wanted to go Iris tumor grew doesn t supply blood to the tumor Cells ProduceAngiogenesis Stimulating Molecules Vasc 1 Cancer cells surrounded by filter with tiny pores 2 Place chamber containing cancer cells beneath the animal s skin 3 Blood vessels growth angiogenesis occurs outside chamber If you put a tumor with tissue flow that carries the tumor near blood supply blood vessels grow towards cancer cells 1 Cancer cells produce VEGF a signaling protein that promotes the growth of new blood vessels go towards Receptor 2 Receptor produces a signal that is recognized by endothelial cells as starving tissue so it turns on genes and the genes get activated proliferate and migrate this is in attempt to get blood vessels to tissue The bigger it gets the more it takes from you take nutrients away from our body Treating Cancer by Inhibition ofAngiogenesis objective to see if we can block shrink cancer Experiment 1 The normal mouse was more affected than the mouse that was
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