Math Biology Seminar: Sumreen Javed

Breast cancer remains the second leading cause of cancer-related death with metastasis accounting around 90% of the total deaths. Specialized subcellular structures termed invadopodia play a critical role in metastasis, aiding tumor cell dissemination to distant sites. Invadopodia have documented roles in aiding tumor cells movement into (intravasation) and out of (extravasation) the blood vessels. While movement through the hematogenous system is well characterised, we are limited in our understanding of dissemination through the lymphatics. In this study we explore the role of invadopodia in aiding tumor cells invasion through the lymphatics. To impair invadopodia formation, knockout (KO) of key invadopodial regulatory protein Tks5 was performed in human breast cancer cells MDA-MB-231. Invadopodia formation in Tks5-KO cells was found to be completely abolished. We assessed cell invasion across a lymphatic monolayer and found a significant reduction in lymphatic invasion for Tks5-KO cells. Next, using transendothelial electrical resistance (TEER) we measured lymphatic tight junction integrity and found that control cells were able to reduce lymphatic tight junctions but this was significantly impaired in Tks5-KO. Overall, the inability of Tks5-KO cells to form invadopodia compromised their ability to invade through the lymphatics suggesting that invadopodia aid tumor cells invasion through the lymphatic system. Current studies are expanding on this work to better understand the role of invadopodia in lymphatic dissemination through the use of live cell imaging and bioluminescent imaging of progression and lymphatic invasion in mice.