# Systemic regulation of metastasis

> **NIH NIH R35** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $996,660

## Abstract

Project Summary
Cancer is a systemic disease. Its growth and malignant progression relies not only on the intrinsic aberrant
genetic and epigenetic makeup of tumor cells, but also on the tumor-induced systemic factors which impact
cells in local and distant microenvironments. Importantly, there is dynamic crosstalk between the tumor-
educated tissues and organs and the tumor itself, especially during metastatic progression. As the tumor
reshapes its local microenvironment, coaxing it to support cancer growth, it exerts systemic effects, conquering
the immune system and distant organs, leading not only to metastasis but also to vascular changes (vascular
leakiness, coagulation), muscular and metabolic changes (cachexia), liver and lung failure, changes in bone
density (osteoporosis or osteopetrosis), and neuropathies, but maybe above all, inflammation and immune
suppression. The tumor exerts its systemic effects, coaxing the various organ systems of the host to support
cancer growth through tumor-secreted factors, such as soluble factors (cytokines and chemokines) and
exosomes (and exomeres, the novel particles we recently discovered) nanovesicles that carry complex cargo,
including proteins, metabolites, DNA and coding as well as non-coding RNAs. The development of effective
anti-metastatic therapies is predicated on our understanding of these iterative and complex interactions
between the tumor and its host, and on devising ways to interrupt this communication. We developed novel
approaches to analyze the heterogeneity and functional roles of tumor-derived exosomes and exomeres in
metastasis as well as their capacity to induce systemic changes. Ultimately, we propose to explore the
possibility that inhibition of specific exosome cargo molecules or their targets in hematopoietic cells could
reverse immunosuppression, pre-metastatic niche formation and the systemic effects of cancer. In summary,
we will focus on studying the mechanisms through which exosomes and exosomes regulate immune system
mobilization, metabolic changes and plasticity of pre-metastatic and metastatic niches in cancer models and
patients.

## Key facts

- **NIH application ID:** 10463609
- **Project number:** 5R35CA232093-05
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** DAVID CHARLES LYDEN
- **Activity code:** R35 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $996,660
- **Award type:** 5
- **Project period:** 2018-09-18 → 2025-08-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10463609

## Citation

> US National Institutes of Health, RePORTER application 10463609, Systemic regulation of metastasis (5R35CA232093-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10463609. Licensed CC0.

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