Effects of the ECM on Lung Cancer Metastasis

In the West Lab, we have used the PEG hydrogel system as a means to simulate cancer cell microenvironments.  PEG hydrogels offer an advantage over other previously used scaffold materials, like Matrigel and collagen, because we are able to independently control their mechanical and biochemical properties.  Using this system, we can probe how specific extracullar matrix factors influence cancer cell behavior and gain a better understanding of how cancer cells develop and metastasize.

People:

Laila Roudsari

My project focuses on studying metastasis and angiogenesis in lung cancer.  More specifically, I am interested in how the properties of the extracellular matrix influence the morphology of model lung adenocarcinoma cells with varying metastatic capacties.  Incorporation of these cells into bioactive PEG matrices allows for a high degree of control over cell-matrix interactions as well as the ability to tune the mechanical properties without changing the material composition. 

This PEG hydrogel platform is also being utilized to incroporate model lung adenocarcinoma cells with microvascular cells to build a model of tumor angiogenesis.  In order for a tumor to become metastatic, it must recruit its own blood supply in a process known as tumor angiogenesis, whereby the vasculature provides nutrients and waste removal but also serves as a route for tumor cells to spread to distant sites.  Thus a solid understanding of the process of angiogenesis is critical to understanding tumor progression to a metastatic phenotype.  The angiogenesis model I am working on facilitates the study of how the microvasculature changes when interacting with different cancer cells and furthermore allows for the assessment of the changes in cancer cell morphology during the angiogenesis process.  My ultimate goal is to utilize this model to test potential anti-angiogenic therapeutic agents for cancer treatment.

 


Left: Schematic of tumor angiogenesis model showing the dual gel method approach, whereby cancer cells are encapsulated in one gel and angiogenic cells (endothelial and pericyte cells) are encapsulated in an adjacent gel

Right: Phase contrast image of a dual gel showing angiogenic cells invading a cancer gel (Scale bar = 100 μm).

Dual Gel SchematicDual Gel Phase

 

 

 

 

 

 

 

 

Murine model of metastatic lung adenocarcinoma in degradable, cell-adhesive PEG hydrogels showing the formation of a lumenized sphere with epithelial polarity (stained with polarity markers, β-catenin, ZO-1, and DAPI) (Scale bar = 20 μm).

344sq cells lumenized

Recent Publications:

  1. Gill BJ, Gibbons DL, Roudsari LC, Saik JE, Rizvi ZH, Roybal JD, Kurie JM, West JL.  A Synthetic Matrix with Independently Tunable Biochemistry and Mechanical Properties to Study Epithelial Morphogenesis and EMT in a Lung Adenocarcinoma Model. Cancer Research. 72(22), 6013 - 6023.