Publications

Publications

Invadopodia Are Required for Cancer Cell Extravasation and Are a Therapeutic Target for Metastasis

By:
Contributors: John D. Lewis Research Group, Katia Carmine-Simmen, PhD, Konstantin Stoletov, PhD

Cell Rep. 2014 Sep 11;8(5):1558-70. doi: 10.1016/j.celrep.2014.07.050. Epub 2014 Aug 28.

Leong HS1, Robertson AE1, Stoletov K2, Leith SJ1, Chin CA1, Chien AE1, Hague MN3, Ablack A1, Carmine-Simmen K2, McPherson VA1, Postenka CO3, Turley EA4, Courtneidge SA5, Chambers AF3, Lewis JD6.

 

Abstract
Tumor cell extravasation is a key step during cancer metastasis, yet the precise mechanisms that regulate this dynamic process are unclear. We utilized a high-resolution time-lapse intravital imaging approach to visualize the dynamics of cancer cell extravasation in vivo. During intravascular migration, cancer cells form protrusive structures identified as invadopodia by their enrichment of MT1-MMP, cortactin, Tks4, and importantly Tks5, which localizes exclusively to invadopodia. Cancer cells extend invadopodia through the endothelium into the extravascular stroma prior to their extravasation at endothelial junctions. Genetic or pharmacological inhibition of invadopodia initiation (cortactin), maturation (Tks5), or function (Tks4) resulted in an abrogation of cancer cell extravasation and metastatic colony formation in an experimental mouse lung metastasis model. This provides direct evidence of a functional role for invadopodia during cancer cell extravasation and distant metastasis and reveals an opportunity for therapeutic intervention in this clinically important process.

PubMed

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New platform for prostate cancer diagnosis to be presented at ISEV 2017

The Lewis Research Group will present exciting results about new blood tests for prostate cancer during 3 talks at the upcoming 2017 International Society of Extracellular Vesicles (ISEV) annual meeting in Toronto (May 18-21). ISEV is a global society of researchers studying exosomes and microvesicles, which are the exciting new focus of cancer therapy and diagnosis.

Dr. Desmond Pink will speak about “Microflow cytometry: The Apogee A50 is a sensitive standard tool for extracellular vesicle analyses in liquid biopsies”, Robert Paproski’s presentation is entitled “Using machine learning of extracellular vesicle flow cytometry to build predictive fingerprints for prostate cancer diagnosis”, and Dr. John Lewis will speak about “An extracellular vesicle blood fingerprint distinguishes between patients with indolent and aggressive prostate cancer at diagnosis”.

The team is looking forward to sharing these key advances that were made possible through the APCaRI prospective cohort.

- John Lewis