# A platform to functionally sort and analyze tumor cells within combinatorial metastatic micorenvironments

> **NIH NIH R01** · UNIVERSITY OF MINNESOTA · 2020 · $598,441

## Abstract

Metastases are responsible for ~90% of human cancer-related deaths, yet our understanding of the stages of
metastasis and the regulating features that drive secondary, tertiary etc. tumors is sorely lacking. In particular,
the early niche surrounding disseminated cells appears critical for survival, dormancy, and/or successful
development of progressing micrometastases. Indeed, not infrequently, breast cancer patients succumb to
recurrent or metastatic disease years to decades after treatment that had rendered the disease undetectable.
In fact, greater than 67% of breast cancer deaths occur beyond the 5-year survival window and some patients
present with recurrence after more than a decade of being “disease-free”. Yet, our understanding of the
intrinsic and environmental factors that initiate and maintain programs of dormancy versus metastatic
progression remains extremely limited. Here, we seek to elucidate fundamental physical and molecular
mechanisms that govern cell fate in ectopic sites. To date, numerous technical hurdles have impeded our
ability to study the genetic and microenvironmental drivers of dormancy and recurrence, particularly in vivo
where these events are rare and not easily controlled. Indeed, in vitro platforms that permit control of the cell
microenvironment and permit cell isolation based on cell state (i.e. dormant vs. progressing) are required to
identify and characterize molecular mechanisms governing these behaviors that can be validated and targeted
in vivo. To address these significant challenges, this proposal leverages expertise in cancer biology and cancer
bioengineering through numerous innovative technologies (e.g. microfluidic generation of metastatic niches,
advanced optical imaging, cutting edge cell engineering with CRISPR technologies etc.) that uniquely enable
us to drastically improve our understanding of how dormancy is regulated in vivo. Here, we hypothesize that
dormancy or colony proliferation in metastatic niches is dictated by lock-and-key behavior between cancer cells
with specific genetic and epigenetic signaling and the initial and evolving properties of the ectopic
microenvironment. Our hypotheses will be tested in the following Specific Aims: (1) Define specific
extracellular matrix compositions that drive survival, dormancy, or colonization using high-throughput micro-
engineering metastatic environments (MEME) technology; (2) Dissect the molecular mechanisms governing
survival, dormancy, or colonization in defined metastatic niche microenvironments; (3) Define the specific
influence of bone marrow-derived and tissue-specific resident macrophages in carcinoma cell survival,
dormancy, or colonization. Through these efforts we will dissect the mechanistic drivers of disseminated tumor
cell dormancy or proliferation, which will elucidate therapeutic targets to prevent dormant tumor cells from
evading therapy. Additionally, these studies will reveal therapeutic targets to kill dormant cells directl...

## Key facts

- **NIH application ID:** 10051222
- **Project number:** 1R01CA245550-01A1
- **Recipient organization:** UNIVERSITY OF MINNESOTA
- **Principal Investigator:** Paolo Provenzano
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $598,441
- **Award type:** 1
- **Project period:** 2020-05-08 → 2025-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10051222

## Citation

> US National Institutes of Health, RePORTER application 10051222, A platform to functionally sort and analyze tumor cells within combinatorial metastatic micorenvironments (1R01CA245550-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10051222. Licensed CC0.

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