Zoey Tan
Pronouns: she/her
Research Mentor(s): Jesus Ramon Ocadiz Ruiz
Research Mentor School/College/Department: BME / Engineering
Program: UROPF
Session: Session 3 (11:00am – 11:50am)
Authors: Zoey Tan, Ramon Ocadiz Ruiz
Abstract
Current breast cancer metastasis detection screening tools are based on imaging technology, such as high-resolution Computed Tomography (CT), MRI, and Positron Emission Tomography (PET), that can identify tumors that have reached a detectable size. However, this technology carries side problems, including the steep cost and high false-positive rates that lead to follow-up tests and invasive procedures that confer additional risks to patients. Biopsies are a common method of detecting metastatic cancer cells in the body. While effective in most cases, biopsies are very difficult to perform in hard to access sites like the lungs or bone marrow. We have developed a new approach for breast cancer metastasis surveillance based on a porous bioengineered implant (scaffold) that can become infiltrated by immune cells and subsequently tumor cells, acting as a surrogate metastatic tissue. We hypothesize that the scaffold detects changes in distal tissue in response to primary tumor generation, providing information about tumor cell phenotype, immune cells, and the metastatic microenvironment. We implanted scaffolds in immunocompromised mice inoculated with human breast cancer cells lines. After 21 days, tissues from primary tumor, lung, and scaffolds were surgically extracted and processed into a single-cell suspension to generate conditioned media (CM). Then tumor cells were incubated in CM derived from tumor-free or tumor bearing mice. We next investigated the transcriptional activity associated with an epithelial to mesenchymal transition (EMT) using a TRanscriptional Activity Cell aRray (TRACER). Our results show that the scaffold recapitulates the lung microenvironment effect in the tumor cell phenotype, confirming that the scaffold effectively reflects the properties of the natural metastatic niche. Additionally, we found that both the lung and the scaffold conditioned media promoted a high and sustained transcription factor activity associated with epithelial–mesenchymal transition, suggesting that the metastatic microenvironment can modify the phenotype of the cancer cells to promote migration. In clinical settings, we envision the use of these bioengineered implants for early cancer recurrence detection and to identify personalized therapeutic strategies to improve patient outcome.
