# Understanding PPARgamma signaling in melanoma brain metastasis

> **NIH NIH R01** · WISTAR INSTITUTE · 2024 · $387,081

## Abstract

Project Summary
Metastasis, the spread of cancer from primary tumor site to distal organs, is the cause of over 80% of deaths
from cancer. The brain is one of the common metastasis locations. Brain metastasis, which develops in the late
course of illness, has become a significant problem in clinic due to its rising incidence as a consequence of
prolonged survival and limited efficacy of existing systemic therapies. Metastasis is a multi-step process that
requires the complex interplay between cancer cells and the stromal cells, a process commonly referred to as
“seed and soil hypothesis” coined over a century ago. The ‘soil’, the microenvironment, not only decides the
outgrowth of metastatic cancer cells, but also contributes to therapy resistance. The ‘seed’, the invaded cancer
cells, directly modifies the surrounding brain stromal cells. Our long-term goal is to dissect the complex
interactions between cancer cells and brain stromal cells during metastasis.
We have developed novel in vivo and in vitro models to address the gaps in our understanding of brain
microenvironmental control of metastatic outgrowth. Our data implicate that astrocytes, the unique and most
abundant brain cells, activate PPARγ signaling in brain metastatic melanoma cells. Through an integrative
approach using in vitro co-culture assays and in vivo brain metastatic mouse models, Aim 1 will delineate the
role of PPARγ pathway in melanoma cells during brain metastasis. We will track the dynamic changes and effect
of PPARγ signaling in melanoma cells throughout the whole brain metastatic process. Moreover, PPARγ
antagonist will be used in our pre-clinical mouse models to test its potential to treat melanoma brain metastasis.
Aim 2 will address how astrocytes activate PPARγ signaling in the invades melanoma cells. We hypothesize
that astrocytes serve as ‘donor’ of unsaturated fatty acids, natural agonist of PPARγ, to the invaded melanoma
cells. The gained insights may enable us to mechanistically deconstruct melanoma brain metastasis and develop
new treatment strategies for patients with little clinical recourse.

## Key facts

- **NIH application ID:** 10738816
- **Project number:** 5R01CA241490-05
- **Recipient organization:** WISTAR INSTITUTE
- **Principal Investigator:** Qing Chen
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2024
- **Award amount:** $387,081
- **Award type:** 5
- **Project period:** 2019-12-01 → 2024-10-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10738816

## Citation

> US National Institutes of Health, RePORTER application 10738816, Understanding PPARgamma signaling in melanoma brain metastasis (5R01CA241490-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/10738816. Licensed CC0.

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