Tumor Microenvironment (TM)

Select Recent Accomplishments

This is an accordion element with a series of buttons that open and close related content panels.

Cell-ECM Interactions

The extracellular matrix is an active participant in cancer, influencing initiation, progression, and response to therapy. A long-standing focus and strength of the TM program has been to understand both the structural and signaling roles of the matrix in cancer.

  • Campagnola, and Patankar (DT) identified collagen structure as a prognostic biomarker in ovarian cancer with 83-91% accuracy rate which is superior to current clinical performance
  • Cryns examined the role of matrix detachment in regulation extracellular-signal regulated kinase (ERK) activity. ERK inhibition can mimic matrix detachment to manipulate circulating tumor cells
  • Keely and Schuler (DT) examined how increased collagen density impacts breast tumor cell response to prolactin demonstrating that prolactin treatment resulted in increased proliferation, invasion, and cross-talk with estrogen when the tumor cells were cultured in dense collagen

Engineering Successes

The integration of engineers into the UWCCC and particularly the TM program is a strength that has allowed us to be a leader in the application of engineering approaches to biomedical research broadly and cancer research specifically.

  • Campagnola, Eliceiri, and Patankar (DT) use nanofabrication to create models of ECM at nano and micro scale
  • Beebe developed innovative models of tissue structure at micro and macro scales to more accurately identify the influence of interventions
  • Masters used a novel biomaterial to independently tune ECM stiffness while concentration is held constant
  • Wilke, Beebe, and Burkard (GEM) designed implantable device that allows for drug diffusion and evaluation in the native environment for more effective treatment selection
  • Skala developed new methods in microscopy to monitor cell-level metabolism in tumors in vivo.

Intercellular Interactions

Recent advancements in understanding the immune system has led to discoveries in the ways tumor cells restrict an anti-tumor immune response through the immune checkpoint, which has led to a host of new therapeutic agents. Moreover, the host immune system can be co-opted by the tumor to serve a protumorigenic role.

  • Rakhmilevich and Sondel (DT) investigated optimal immunotherapies for multiple myeloma to explore the role of immune cells in therapeutic response
  • Eliceiri, and Keely advanced the field’s ability to identify and study immune components through non-invasive autofluorescence imaging to quantify both tumor and immune cell response in vivo
  • Kreeger and Patankar (DT) developed a novel co-culture system to examine paracrine interactions in order to better understand how macrophages impact tumor cells
  • Huttenlocher used zebrafish model to further explore tumor regulation of neutrophil recruitment and quantify the earliest stages of macrophage infiltration
  • Keely, Wilke, and Burkard (GEM) developed trial for treating tumors in a dense collagen environment