# Progression of DCIS to Invasive Breast Cancer through CCR2 Chemokine Signaling

> **NIH NIH R01** · UNIVERSITY OF KANSAS MEDICAL CENTER · 2022 · $471,581

## Abstract

ABSTRACT
About 50,000 cases of ductal carcinoma in situ (DCIS) are diagnosed in the US every year, making DCIS the
most common type of non-invasive breast cancer diagnosed in women. Up to 20% of all patients will experience
disease recurrence accompanied by invasive ductal carcinoma (IDC). Current cyto- and histopathological
approaches do not accurately predict disease progression, resulting in patients being under-treated or over-
treated for DCIS. Our long-term goals are to identify key factors that lead to IDC that will enable the development
of a molecular based approach to predict the risk of IDC, and a more tailored approach to treat DCIS. The
chemokine receptor CCR2 is a G Protein Coupled Receptor, which is normally expressed on macrophages and
regulates chemotaxis in response to CCL2 during inflammation and cancer progression. Using a mammary
intraductal injection model (MIND) to mimic DCIS formation in animals, we have challenged current paradigms
on CCL2/CCR2 signaling, by demonstrating that CCL2/CCR2 signaling to breast cancer cells promotes DCIS
progression to IDC. This R01 renewal project characterizes the role of metabolism and c-MET in CCL2/CCR2
mediated DCIS progression, and may identify better predictive markers for DCIS progression, with implications
on reducing patient over-treatment, and provide justification for developing CCR2 as a therapeutic target to
reduce under-treatment. Metabolic reprogramming is an important hallmark of cancer, but is poorly understood
in early stage breast cancer. Preliminary studies indicate that CCL2/CCR2 enhancement of DCIS progression is
associated with increased glycolysis and glutamine metabolism, which facilitate fatty acid synthesis. CCL2
mediated breast cancer invasiveness and metabolism may be dependent on interactions between CCR2 and c-
MET receptor tyrosine kinases in breast cancer cells. We hypothesize that CCL2/CCR2 chemokine signaling in
breast cancer cells enhances glucose and glutamine metabolism through c-MET dependent mechanisms to
facilitate DCIS progression. Aim 1 is to determine the relevance of CCL2, CCR2, c-MET and metabolic enzyme
expression to DCIS progression to invasive carcinoma using patient samples and magnetic resonance
imaging/spectroscopy approaches in DCIS bearing animals. Aim 2 is to determine the functional contribution of
c-MET to CCL2/CCR2 mediated breast cancer growth, survival, invasion and metabolism through modulating c-
MET in breast cancer cells in vitro and in the MIND model. Mechanisms of CCR2/c-MET/SRC interactions in
breast cancer cell lines will be examined through molecular and biochemical approaches. Aim 3 is to determine
the biochemical and molecular mechanisms through which CCL2/CCR2 mediated metabolic changes promote
breast cancer growth, survival and invasion through modulation of glycolytic, glutamine and fatty acid synthesis
pathways in breast cancer cells in biochemical and cell culture assays. Protein degradation pathways that
potentially ...

## Key facts

- **NIH application ID:** 10407062
- **Project number:** 5R01CA172764-08
- **Recipient organization:** UNIVERSITY OF KANSAS MEDICAL CENTER
- **Principal Investigator:** Nikki Cheng
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $471,581
- **Award type:** 5
- **Project period:** 2013-09-01 → 2025-05-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10407062

## Citation

> US National Institutes of Health, RePORTER application 10407062, Progression of DCIS to Invasive Breast Cancer through CCR2 Chemokine Signaling (5R01CA172764-08). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10407062. Licensed CC0.

---

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