Cell cell contact or via secreted signals sc interact

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cell-cell contact or via secreted signals -SC interact with the niche cells -Differentiation occurs as the cells move away from the niche cells White= HSC Green= Bone-forming cells Red= Blood Vessels
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8 22 Stem Cells and Cancer Cancers display similar characteristics as stem cells Extensive proliferative potential Differentiate into different cell types BUT Cancers have lost much of the normal regulation that keeps stem or differentiated cells in check Proliferation is mostly unchecked Apoptosis is inhibited Differentiation is blocked Changes to normal cellular regulation Signal transduction Cell cycle checkpoints Apoptosis Cell cycle Cell motility 23 Characterization of Human Tumors: In situ Gross Morphology Histology 24
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9 Characterization of Human Tumors: In vitro Cellular transformation- ability of cells to grow indefinitely in the absence of growth factors on a variety of extracellular substrates Cell culture conditions mimic in vivo conditions -food/energy source -signal to grow (growth factors) -extracellular substrate 25 Xenografts- introduction of cells from one species into another (ex. Human into mouse) Why use xenograft models? Unlike cell culture, cells are analyzed in the context of an organism -Cells are in similar environment as in the patient -in vivo specific processes: invasion or metastasis into other organs blood vessel growth (angiogenesis) New models allow following of tumor behaviors in real-time (can’t do this in human patients) Characterization of Human Tumors: in model organisms-- xenograft models 26 What is the genetic component of a human tumor that makes it tumorigenic? Put pieces of human DNA from tumor cells into normal mouse cells Test which pieces induce tumor formation in the normal mouse cells Isolate human DNA Sequence to determine the affected gene Determining the genetic basis of human tumors: identifying tumor causing mutations 27
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10 Determining the genetic basis of human tumors 28 Determining the genetic basis of human tumors 29 Modern methods to identify regions: Cancer sequencing project Isolate tumor samples Purify genomic DNA from samples Construct genomic DNA library of tumor DNA Sequence entire genome to find mutations 30
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11 Cellular pathways affected in cancer 31 Tumor inducing mutations fall into 3 categories 32 Oncogenic mutations in growth factor signaling lead to unregulated cell proliferation Proliferation Gain-of-Function Mutations Ex. mutations in Ras GTPase domain that make it less effective at hydrolyzing GTP What other mutations might lead to gain-of- function hyper proliferative phenotypes?
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