By Weigang wang sumanta goswami Erik sahai jeffrey b wyckoff Jeffrey E Segall and John S Condeelis Presented By Lana Awad and Sebastian Lukjan Motivation of research why they did what they did ID: 322018
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Tumor cells caught in the act of invading: their strategy for enhanced cell motilityBy: Weigang wang, sumanta goswami, Erik sahai, jeffrey b wyckoff, Jeffrey E. Segall and John S. Condeelis
Presented By: Lana
Awad
and Sebastian LukjanSlide2
Motivation of research, why they did what they did…Understand steps that cancer cells take to spread.Want to relate gene expression pattern with likelihood of metastasis- diagnosticsUltimate goal is to find strategies to slow spread of tumor cells - therapeuticsCurrent methods to study cancer metastasis had limitations
http://en.wikipedia.org/wiki/File:Secondary_tumor_deposits_in_the_liver_from_a_primary_cancer_of_the_pancreas.jpg#fileSlide3
Analysis of Primary whole tumorProblem: average expression patterns in all diverse tumor cells and isn’t indicative of invading cells.Wang et alSlide4
Analysis of cells isolated from fixed tumorProblem: metastatic cells are identified by morphological characteristics in fixed tissueWang et alSlide5
Analysis of metastases tumorProblem: Needs to be cell cultured and In vitro conditions may affect gene conditions differently than in vivo conditionsWang et alSlide6
Our Method, catching tumor cells red handed ….. while they are invading using chemotaxisChemotaxis toward blood vessels enhances metastasisGrowth Factor concentration gradient directs invasive cells to blood vesselsTumor cells express more EGF receptors and respond to this gradient betterSlide7
Their Method:In vivo Invasion AssayUsed chemotaxisChemotaxis to blood vessels enhances metastasisUsed a microneedle with known chemo attractants for metastasisThen used microarrays to study gene experssion patternsIn particular looked for change in gene regulation with genes that affected motility Slide8
Paracrine ChemotaxisCarcinoma cells (CC) produce CSF-1 to drive Tumor Associated Macrophages (TAM) to blood vesselTAM procedures EGF to direct CC towards the blood vesselWang et alSlide9
Gene Expression Trends mRNA levels for genes related to mobility affectedmRNA levels for genes related to cell polarity affectedSlide10
A key Discrepancy in Cancer ModelsGene expression results indicate the possibility that metastasis can occur in early tumorsLead to the questioning of current model of cancerSlide11
Hypothesis: Tumor Microenvironment Invasion ModelWang et alSlide12
Key Hypothesis FacetsNovel :Transient gene expression changesMetastasis can occur at earlier or later timesMicroenvironments play a direct role in cell invasionHypothesis still needs to be testedIn situ hybridizationSlide13
Significance to Cancer researchPotential therapeutic agents to prevent metastasis characterize behavior of metastatic tumors on the cellular level.Utilize this understanding to create better therapeutic agentsSlide14
The End