# Exosome secretion in breast cancer progression

> **NIH NIH R01** · VANDERBILT UNIVERSITY · 2021 · $468,221

## Abstract

Exosomes are small extracellular vesicles (EVs) that drive cancer metastasis through paracrine
and autocrine signaling. While the role of specific exosome cargoes in this process is not well
understood, integrin adhesion receptors have been shown to be involved in the choice of
metastatic site. How this occurs is not entirely clear, but could involve binding of exosome-
carried integrins to cognate extracellular matrix (ECM) ligands in distant tissues. Another non-
exclusive possibility is that exosomal integrins and other adhesion receptors directly initiate
assembly of ECM to allow cancer cell survival and invasion at primary tumor sites and
colonization of distant metastatic sites. We will investigate these possible functions of
exosomes in breast cancer metastasis.
 In the prior grant cycle, we identified fundamental mechanisms by which both cancer-
and stromal-derived exosomes control tumor aggressiveness, including: 1) autocrine promotion
of cancer cell migration; 2) fibroblast exosomes are necessary and sufficient to induce assembly
of fibronectin and other stromal matrix proteins, both in vitro and in vivo; 3) and fibroblast-
secreted exosomes promote both growth and metastasis of primary breast tumors. In addition,
we find that adhesion receptors are enriched on small EVs from both cancer cells and
fibroblasts. Based on these other findings, we propose the central hypothesis that adhesion
molecules carried by breast cancer and fibroblast exosomes drive multiple steps of the
metastatic cascade. To test this hypothesis, we will: 1) Test the hypothesis that clustering of
integrins and syndecans within exosomes mediates fibronectin (FN) assembly; 2) Test the
hypothesis that breast cancer cell exosomes carry unique adhesion molecules that can induce
assembly of epithelial-type ECM; 3) Determine the role of exosomal adhesion receptors in
promoting breast cancer metastasis.

## Key facts

- **NIH application ID:** 10234721
- **Project number:** 2R01CA206458-06
- **Recipient organization:** VANDERBILT UNIVERSITY
- **Principal Investigator:** Suzanne Marie Ponik
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $468,221
- **Award type:** 2
- **Project period:** 2016-04-15 → 2026-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10234721

## Citation

> US National Institutes of Health, RePORTER application 10234721, Exosome secretion in breast cancer progression (2R01CA206458-06). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10234721. Licensed CC0.

---

*[NIH grants dataset](/datasets/nih-grants) · CC0 1.0*