# Role of Adenosine in TGF-beta Effects in Cancers

> **NIH NIH R01** · VANDERBILT UNIVERSITY MEDICAL CENTER · 2020 · $361,425

## Abstract

TGFβ and adenosine are ubiquitous molecules in the tumor microenvironment that participate in the
regulation of various stages of tumor progression and metastasis. Our recent studies have demonstrated
an essential role for TGFβ signaling in the differentiation of CD39+CD73+ terminally-differentiated
mononuclear myeloid cells (TDMMC) during tumor progression. We discovered that TDMCCs in tumor
tissue generate high levels of adenosine via unique co-expression of CD39 and CD73 regulated by TGFβ.
Adenosine is a key regulator of inflammation, angiogenesis and immune cell function. Our novel data show
that adenosine generated by TDMMC in a paracrine manner decreases fibroblast responses to TGFβ. Loss
of TGFβ signaling on fibroblasts in tumor tissue correlates with increase metastasis and poor survival of
cancer patients. We hypothesize that that CD39+CD73+ myeloid cells negatively regulate TGFβ effects on
tumor-associated fibroblasts promoting them, via activation of A2 adenosine receptors, to cells with pro-metastatic
and pro-tumorigenic properties. We propose to test this hypothesis in Specific Aim 1 by
examining the functional significance of CD39 and CD73 expression on TDMMC in regulation fibroblasts
functions in vitro. In Specific Aim 2, we will determine the molecular mechanisms of interactions between
adenosine signaling and TGFβ signaling on cancer-associated fibroblasts. Finally, in Specific Aim 3, we will
determine the role of adenosine receptors on fibroblasts in tumor progression, microenvironmental
changes and metastasis. We anticipate that findings from the proposed studies will provide new insight into
the depth and complexity of mechanisms that mediate the effects of adenosine on TGFβ signaling during
tumor progression. Our findings will aid in developing novel therapeutic strategies to decrease tumor
progression and metastases.

## Key facts

- **NIH application ID:** 9959363
- **Project number:** 5R01CA200681-05
- **Recipient organization:** VANDERBILT UNIVERSITY MEDICAL CENTER
- **Principal Investigator:** Sergey V. Novitskiy
- **Activity code:** R01 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2020
- **Award amount:** $361,425
- **Award type:** 5
- **Project period:** 2016-07-01 → 2021-07-19

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/9959363

## Citation

> US National Institutes of Health, RePORTER application 9959363, Role of Adenosine in TGF-beta Effects in Cancers (5R01CA200681-05). Retrieved via AI Analytics 2026-05-25 from https://api.ai-analytics.org/grant/nih/9959363. Licensed CC0.

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