# Developing Adhesome Technology as a Physical Marker of Highly Metastatic Cells

> **NIH NIH R21** · UNIVERSITY OF CALIFORNIA, SAN DIEGO · 2020 · $236,250

## Abstract

Project Summary
Diagnostic markers have improved our ability to identify tumors at earlier stages, but secondary metastases
are still exceedingly common and aggressive. Metastases result from primary tumors shedding a small
subpopulation of stem-like cells that can migrate through adjacent stroma and disseminate throughout the
body unlike those cells remaining in the primary tumor. Progress towards identifying molecular prognostic
markers of these stem-like cells that could assess metastatic risk has been limited; very recently however,
evidence has suggested that a tumor's physical state may act as an alternative prognostic marker . We have
observed that one such physical marker–adhesion strength–varies in metastatic epithelial cell lines from
mammary, prostate, and lung tumors due to differences in focal adhesion assembly in stromal-like conditions,
e.g. low Mg+2 and Ca+2. Thus strongly adherent sub-populations are slower and less processive than their
unselected counterparts. Our hypothesis is that the converse population, i.e. weakly adherent tumor cells in the
stroma, represents the most metastatic sub-population, which can be purified based on their adhesion strength
and counted to determine metastatic risk. To isolate this converse population of weakly adherent cells, we
have developed an “adhesome” flow chamber assay that will subject cells to low shear (<10 dynes/cm2) in
stromal-like environments and rapidly (<10 min) sort 107 cells. Using this technology for proof-of-concept in
Aim 1, we will validate its sorting efficiency and fidelity and observe the potential of weakly adherent cells to
detach, migrate, and invade engineered microenvironments that resemble adjacent tumor stroma. In Aim 2, we
will test the adhesome flow chamber's ability to predict breast cancer metastatic risk in vivo by injecting
selected cells into mammary fat pads. We will then assess the propensity of weakly or strongly adherent cells
to form or not form metastases, respectively. Cells from primary tumor stroma will be directly assessed to
identify cells with a weakly adhesive signature and correlate that with secondary metastasis formation as would
occur in the clinic. By validating across tumor types, this Innovative Molecular and Cellular Analysis
Technologies R21 proposal will establish an adhesome flow chamber technology and validate our hypothesis
that weakly adherent tumor cells are capable of migrating and forming secondary metastases, i.e. establish
metastatic risk. Thus this technology should provide clinicians with addition prognostic assessment of a tumor's
metastatic risk.

## Key facts

- **NIH application ID:** 9922219
- **Project number:** 5R21CA217735-03
- **Recipient organization:** UNIVERSITY OF CALIFORNIA, SAN DIEGO
- **Principal Investigator:** Adam J Engler
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $236,250
- **Award type:** 5
- **Project period:** 2018-05-01 → 2021-04-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9922219

## Citation

> US National Institutes of Health, RePORTER application 9922219, Developing Adhesome Technology as a Physical Marker of Highly Metastatic Cells (5R21CA217735-03). Retrieved via AI Analytics 2026-05-26 from https://api.ai-analytics.org/grant/nih/9922219. Licensed CC0.

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