Tumor Cell Invasion Strategies and Research Methods
Explore the strategies employed by tumor cells for enhanced motility and invasion, as well as the research methods used to study metastasis. Discover how chemotaxis towards blood vessels plays a role in cancer cell spread and the in vivo invasion assay used to analyze gene expression patterns affecting motility.
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Presentation Transcript
TUMOR CELLS CAUGHT IN THE ACT OF TUMOR CELLS CAUGHT IN THE ACT OF INVADING: THEIR STRATEGY FOR INVADING: THEIR STRATEGY FOR ENHANCED CELL MOTILITY ENHANCED CELL MOTILITY BY: BY: WEIGANG WEIGANG WANG SAHAI SAHAI, , JEFFREY JEFFREY B B WYCKOFF AND JOHN S. AND JOHN S. CONDEELIS CONDEELIS WANG, , SUMANTA SUMANTA GOSWAMI WYCKOFF, JEFFREY E. , JEFFREY E. SEGALL GOSWAMI, ERIK , ERIK SEGALL Presented By: Lana Awad and Sebastian Lukjan
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- diagnostics Ultimate goal is to find strategies to slow spread of tumor cells - therapeutics Current methods to study cancer metastasis had limitations http://en.wikipedia.org/wiki/F ile:Secondary_tumor_depos its_in_the_liver_from_a_pri mary_cancer_of_the_pancr eas.jpg#file
Analysis of Primary whole tumor Problem: average expression patterns in all diverse tumor cells and isn t indicative of invading cells. Wang et al
Analysis of cells isolated from fixed tumor Problem: metastatic cells are identified by morphological characteristics in fixed tissue Wang et al
Analysis of metastases tumor Problem: Needs to be cell cultured and In vitro conditions may affect gene conditions differently than in vivo conditions Wang et al
Our Method, catching tumor cells red handed .. while they are invading using chemotaxis chemotaxis Chemotaxis toward blood vessels enhances metastasis Growth Factor concentration gradient directs invasive cells to blood vessels Tumor cells express more EGF receptors and respond to this gradient better
Their Method: In vivo Invasion Assay Used chemotaxis Chemotaxis to blood vessels enhances metastasis Used a microneedle with known chemo attractants for metastasis Then used microarrays to study gene experssion patterns In particular looked for change in gene regulation with genes that affected motility
Paracrine Chemotaxis Carcinoma cells (CC) produce CSF- 1 to drive Tumor Associated Macrophages (TAM) to blood vessel TAM procedures EGF to direct CC towards the blood vessel Wang et al
Gene Expression Trends mRNA levels for genes related to mobility affected mRNA levels for genes related to cell polarity affected
A key Discrepancy in Cancer Models Gene expression results indicate the possibility that metastasis can occur in early tumors Lead to the questioning of current model of cancer
Hypothesis: Tumor Microenvironment Invasion Model Wang et al
Key Hypothesis Facets Novel : Transient gene expression changes Metastasis can occur at earlier or later times Microenvironments play a direct role in cell invasion Hypothesis still needs to be tested In situ hybridization
Significance to Cancer research Potential therapeutic agents to prevent metastasis characterize behavior of metastatic tumors on the cellular level. Utilize this understanding to create better therapeutic agents
