# Heterogeneity of the Early Metastatic Niche in Cancer Progression and Chemoresistance

> **NIH NIH F32** · UNIVERSITY OF MICHIGAN AT ANN ARBOR · 2021 · $68,562

## Abstract

Project Summary
For many types of cancer, the formation of distant metastasis marks the disease stage where treatment is no
longer curative. Currently, there are limited methods to detect dissemination and colonization of tumor cells to
distal sites until macroscopic tumors are radiologically evident. To improve detection of metastasis at early and
more treatable stages, we developed biomaterial scaffolds that recruit breast metastatic tumor cells in mouse
models, acting as a diagnostic. Our long-term objective is to use the scaffolds as a tool for the early
detection of metastatic disease and to monitor the niche environment to determine responsiveness to
therapy. We propose to employ the scaffold to dissect cellular components that mediate tumor cell recruitment
and phenotype, prior to and following therapy. Implantable scaffolds recruit tumor cells in vivo prior to their
detection in solid organs. The recruitment of tumor cells to a defined site serves as a defined and accessible
location to detect metastatic progression and facilitates study into mechanisms of niche development. Tumor
cells isolated from the scaffold have distinct migration, invasion, and dissemination behaviors relative to cells
isolated from the primary tumor but are phenotypically similar to those found in the lung. Elements reported in
the natural metastatic niche, including myeloid derived suppressor cells and macrophages, have been found
within the implanted scaffolds. Clear changes in the populations of immune cells at the scaffold were identified
as metastatic disease progressed. We propose the following specific aims. Specific Aim 1 will investigate the
cellular composition and heterogeneity of implant-captured cells during disease progression.
Implantable scaffolds recruit tumor cells in vivo before their detection at other metastatic sites. We propose to
dissect the cellular composition of both physiologic and synthetic niches through single cell analyses, and to
assess their contribution to tumor cell recruitment. The phenotypes and heterogeneity of these cells will be
monitored over time to determine sub-populations that can predict the status of the physiologic metastatic niche.
Specific Aim 2 will test the hypothesis that the scaffolds can monitor responsiveness to therapy.
Therapeutic resistance occurs with even the most promising drugs, largely due to heterogeneity of the tumor
cells. Aim 2 will correlate tumor and stromal cell phenotypes in the synthetic niche with survival outcomes in the
mice following treatment with eribulin chemotherapy. We will identify specific genes and cell phenotypes that are
highly differentiated between responsive and resistant mice. Specific Aim 3 will investigate safety and cell
recruitment in the scaffolds in a Phase I clinical trial. We propose to implant scaffolds in adult females
diagnosed with metastatic breast cancer to evaluate the potential of the scaffolds as a clinical diagnostic. The
safety of the scaffolds will be as...

## Key facts

- **NIH application ID:** 10148738
- **Project number:** 5F32CA243421-03
- **Recipient organization:** UNIVERSITY OF MICHIGAN AT ANN ARBOR
- **Principal Investigator:** Sophia M Orbach
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $68,562
- **Award type:** 5
- **Project period:** 2019-07-01 → 2022-06-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10148738

## Citation

> US National Institutes of Health, RePORTER application 10148738, Heterogeneity of the Early Metastatic Niche in Cancer Progression and Chemoresistance (5F32CA243421-03). Retrieved via AI Analytics 2026-05-28 from https://api.ai-analytics.org/grant/nih/10148738. Licensed CC0.

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