Evaluation of the Role of Invadopodia in Lung Cancer Cell Growth and Invasion
Annual rept. 1 Nov 2013-31 Oct 2014
SANFORD-BURNHAM MEDICAL RESEARCH INST LA JOLLA CA
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Invadopodia are actin-based cellular protrusions found in many invasive cancer cell types. Non small cell lung cancers NSCLCs are highly invasive and metastatic. The high mortality rate of NSCLC is attributable to the finding of overt metastases in the majorityof patients at the time of diagnosis, as well as to the inoperable nature of many tumors. Yet remarkably, no studies have evaluated invadopodia formation and function in lung cancer cells. Unpublished immunohistochemical evidence from our laboratory suggeststhat the invadopodia scaffold protein Tks5 is expressed in the majority of primary NSCLCs, and to particularly high levels in at least 25 of specimens, suggesting that invadopodia may play a role in NSCLC progression. The finding that some fraction or sub-type of NSCLC may use invadopodia as a mechanism of tumor growth and invasion may ultimately have clinical relevance. Our hypothesis is that invadopodia form in NSCLCs as a result of EGFr and KRas signaling and that this in turn promotes invasion andtumor cell growth. We will first evaluate the expression of invadopodia proteins in a panel of NSCLC lines previously phenotyped for EGFr and KRas status. Next we will determine the effect of invadopodia loss on invasion and tumor cell growth in vitro. Finally, we will evaluate the role of invadopodia in tumor growth and metastasis in vivo. This focused yet comprehensive analysis will elucidate the frequency of invadopodia involvement in the invasive behavior of lung cancer cells, and if appropriate, set the stage for more in depth studies.
- Medicine and Medical Research