# (PQ6) vGPCR-Mediated Paracrine Transformation for Kaposi Sarcoma

> **NIH NIH R01** · UNIVERSITY OF SOUTHERN CALIFORNIA · 2022 · $188,374

## Abstract

PROJECT SUMMARY
This project is proposed to respond to Provocative Question 6 in RFA-CA-19-032.
Objective: Paracrine transformation is a theoretical concept that was proposed years ago to explain the
unconventional “non-autonomous” oncogenesis observed during development of Kaposi’s sarcoma (KS), one of
the most common AIDS-associated malignancies. This proposal is designed to prove its existence, to dissect its
mechanism, identify the players therein, and to define its roles in KS tumorigenesis using our novel animal
models and an engineered microphysiological platform.
Rationale: Kaposi’s sarcoma herpes virus (KSHV) causes an endothelial cell tumor, KS, in the skin and internal
organs. A paradox in KS oncogenesis is that while most KS tumor cells are latently infected with minimal viral
gene expression, only lytic-stage cells express vGPCR, the only known viral oncogene that is necessary and
sufficient for KS development.
Provocative Question: How vGPCR, a lytic viral gene expressed in cells destined to die, can cause cancer?
Challenges: This question remained unanswered due to the lack of proper animal models, engineered in vitro
or ex vivo systems to study pathogenesis, persistence, and tumor development that recapitulate this HIV/AIDS-
associated malignancies.
Innovation & Strategy: We have developed a series of novel animal models and Vascularized Skin Chip
platform. Using these technical advancements, we will prove the existence of paracrine transformation, identify
its cellular (immune cells, HIV) and molecular (vGPCR-loaded exosome) players, and characterize its
mechanism as the main oncogenic driver for KS tumorigenesis.
Impact: Our study will address the decades-long conundrum on KS tumor development by defining the
existence and mechanism of paracrine transformation. This provocative concept of paracrine transformation
will not only force us to move our focus beyond the lytic-infected cells as the oncogenic drivers, but also
expand the way we understand the initiation, progression, and metastasis of cancer. In addition, this study will
open a new door to novel anti-KS therapeutics, and provide a solid justification to investigate the presence of
equivalent non-autonomous transformation in other non-viral oncogenesis, such as breast and colon cancers.

## Key facts

- **NIH application ID:** 10524182
- **Project number:** 3R01CA250065-03S1
- **Recipient organization:** UNIVERSITY OF SOUTHERN CALIFORNIA
- **Principal Investigator:** Young-Kwon Hong
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $188,374
- **Award type:** 3
- **Project period:** 2020-08-01 → 2025-07-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10524182

## Citation

> US National Institutes of Health, RePORTER application 10524182, (PQ6) vGPCR-Mediated Paracrine Transformation for Kaposi Sarcoma (3R01CA250065-03S1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10524182. Licensed CC0.

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