# Project 2: Profiling Gene Expression and Mechanophenotype in Circulating Tumor Cells Ex Vivo

> **NIH NIH P20** · BROWN UNIVERSITY · 2021 · $377,375

## Abstract

PROJECT SUMMARY
Primary tumors shed circulating tumor cells (CTCs) into the bloodstream that metastasize
preferentially to distant organs, resulting in 90% of cancer related fatalities. For example, estrogen
receptor positive (ER+) breast cancers exhibit high rates of metastasis to bone, with decreased rates to liver
and lung. CTCs exhibit heterogeneous gene expression programs and functional phenotypes, which are
selected by soluble and mechanical interactions within each metastatic “niche.” A critical challenge is to
predict how patient-specific CTCs disseminate throughout the body and respond to therapeutic treatments. An
exciting strategy is to culture CTCs ex vivo for drug screening informed by genomic and transcriptional profiling.
We seek to elucidate how CTCs respond to different features of the metastatic niche by engineering controlled
interactions with tissue-specific extracellular matrix (ECM) and with human primary stromal cells, which may
recapitulate disease progression and therapeutic resistance in these microenvironmental contexts.
Our long-term goal is to establish preclinical assays for patient CTCs to predict metastatic disease
progression and screen targeted inhibitors. Realization of this goal involves several technical challenges,
including: 1) Tissue-mimetic matrix with tunable biochemistry and mechanics, 2) Multicellular tissue constructs
with controlled size and cellular composition, 3) Gene expression profiling of CTCs in response to soluble and
mechanical stimuli, 4) Spatiotemporal analysis of phenotypic heterogeneity, including the epithelial-
mesenchymal transition (EMT), and 5) Validation with human patient samples. Thus, our overall objective is
to understand how CTC gene expression and mechanophenotype is regulated by matrix or stromal interactions
in tissue-mimetic microenvironments. This discovery-based approach can deconstruct patterns of gene
expression driven by decellularized extracellular matrix or the secretome of human stromal cells. Such
bioinformatics analyses can identify possible therapeutic strategies based on existing patient, xenograft, and
high-throughput screens.
PI: Wong is a New Investigator with expertise in cancer cell migration, biomaterials, and microfluidics. Mentor:
Reichner is an expert on directed cell migration and mechanobiology and Mentor: Bertone is an expert on
single cell analyses in cancer. We investigate the relative contributions of microenvironmental stimuli using
three aims: AIM 1 will elucidate how individual breast cancer cells interact with tissue-mimetic matrix and AIM 2
will engineer co-cultured multicellular spheroids with stromal cells.

## Key facts

- **NIH application ID:** 10271624
- **Project number:** 2P20GM109035-06
- **Recipient organization:** BROWN UNIVERSITY
- **Principal Investigator:** Ian Y Wong
- **Activity code:** P20 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $377,375
- **Award type:** 2
- **Project period:** 2016-06-01 → 2026-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10271624

## Citation

> US National Institutes of Health, RePORTER application 10271624, Project 2: Profiling Gene Expression and Mechanophenotype in Circulating Tumor Cells Ex Vivo (2P20GM109035-06). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10271624. Licensed CC0.

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