# Project 2: Regulation of Tumor Metastasis by Systemic S1P and Complement Signaling

> **NIH NIH P01** · MEDICAL UNIVERSITY OF SOUTH CAROLINA · 2020 · $274,051

## Abstract

SUMMARY 
This project is designed to test a novel hypothesis that cancer cells communicate with the host via C5a/C5aR- 
induced systemic SK1/S1P, which then promotes tumor metastasis, and that inhibition of systemic S1P/C5aR 
signaling suppresses metastasis. To test this hypothesis, three Specific Aims are proposed: Aim 1 is designed 
to define the roles and mechanisms of cancer cell-induced vascular endothelial cell complement signaling and 
systemic SK1/S1P in the regulation of tumor metastasis. Aim 2 is designed to determine the down-stream 
mechanisms by which cancer cell-induced systemic SK-1/S1P promotes tumor metastasis. In this Aim, our 
main goal is to test our hypothesis that cancer cell-induced systemic SK1/S1P inhibits the expression of a 
master suppressor of metastasis (BRMS1) via S1PR2 signaling in cancer cells, inducing tumor metastasis. 
Aim 3 is designed to determine the therapeutic efficacy of targeting systemic S1P and/or C5a signaling for the 
attenuation of tumor metastasis. In this Aim, our main goal is to test a novel hypothesis that inhibition of 
systemic C5aR/SK1/S1P signaling will inhibit tumor metastasis via activation of tumor BRMS1. These studies 
will help uncover how cancer cells communicate with the host via SK1/S1P and complement signaling to 
regulate tumor metastasis, leading to the development of novel therapeutic strategies for the inhibition of tumor 
growth or metastasis. In this project, we will also determine if the elevation of systemic S1P/C5a in patients 
with advanced solid tumors will provide novel serum markers for monitoring response to therapy and/or early 
detection of progression to metastasis.

## Key facts

- **NIH application ID:** 9980709
- **Project number:** 5P01CA203628-05
- **Recipient organization:** MEDICAL UNIVERSITY OF SOUTH CAROLINA
- **Principal Investigator:** Besim Ogretmen
- **Activity code:** P01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $274,051
- **Award type:** 5
- **Project period:** — → —

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9980709

## Citation

> US National Institutes of Health, RePORTER application 9980709, Project 2: Regulation of Tumor Metastasis by Systemic S1P and Complement Signaling (5P01CA203628-05). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/9980709. Licensed CC0.

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