I11 - Utilizing Biophysical Properties of Epithelial Cancer Cells to Predict Metastatic Capacity

Introduction: : Cancer is the second leading cause of death in the United States, and in 2025 over 2,000,000 new cases are projected to be diagnosed. Cancer can affect several types of tissue, making the identification of a universal molecular prognostic marker improbable. Due to this, patients can be underdiagnosed, not receive appropriate treatment, and may develop metastatic disease. Therefore, a new metric to more accurately predict metastatic capacity of epithelial based cancers is needed. Our prior work supports a biophysical marker, adhesion strength, as a more accurate means of stratifying tumor metastatic potential in breast cancer. We now aim to demonstrate that adhesion strength is a universal property that can not only be used to stratify breast cancer cells by their metastatic potential, but also lung/bronchus, prostate, and colon/rectum carcinomas.

Materials and

Methods: : Adhesion strength of established human cell lines from patients with lung/bronchus, prostate, and colon/rectum cancers with varying metastatic capacities, as well as healthy control lines, will be characterized via spinning disc and divergent parallel plate flow chamber assays. The T50, or the shear stress at which 50% of seeded cells are sheared off from their substrate, will be measured and compared amongst lines. Additionally, migration assays on collagen-coated polyacrylamide gels, with tissue matched stiffness, will be conducted to identify the cell speed and displacement of each line. T50 measurements will be plotted against migration data to determine if an inverse correlation between adhesion and migration exists.

Results, Conclusions, and Discussions:: Preliminary adhesion data from highly metastatic/mesenchymal lung cancer NCI-H1299 cells and less metastatic lung cancer A549 cells were collected via the spinning disc assay. Data indicates that the less metastatic A549 cells have a 3-fold higher T50 compared to the more metastatic/mesenchymal NCI-H1299 cells. From this we predict that we will continue to see this trend amongst additional lung cancer cell lines, where the more metastatic the line the more weakly adherent it will be. Additionally, we hypothesize that these trends will also be seen amongst prostate and colon/rectum cancers. We expect that more metastatic cell lines will migrate at higher speeds and displacements on collagen-polyacrylamide gels, and that there exists an inverse relationship between adhesion strength and migration. We hypothesize that adhesion strength is a universal metric amongst epithelial based cancers that can be used to stratify cells based on their metastatic capacities.

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