# Role of phosphate availability in lung cancer invasion and bone metastasis

> **NIH NIH F32** · EMORY UNIVERSITY · 2021 · $79,386

## Abstract

PROJECT SUMMARY
Metastatic dissemination is a leading cause of death from cancer with metastasis to bone represents a
particularly poor prognosis. Unfortunately, metastasis to bone is one of the most common sites of metastases in
cancers such as breast, prostate and lung. In lung cancer, near half of advanced cases develop metastasis to
the bone significantly impacting morbidity and survival. The underlying mechanisms are incompletely understood
limiting treatment options to reducing pain and fracture risk after diagnosis. Therefore, studies addressing this
underserved area would mark a significant advance in preventing and treating bone metastasis. Increasingly
different components of the tumor microenvironment have been identified as modulators of cancer progression.
Ourselves and others have identified one such component to be inorganic phosphate (Pi), which is elevated in
the American diet due to processed foods. High dietary Pi has putatively been linked to cancer progression and
aggression. Our data suggests that high Pi could increase local invasion, angiogenesis and bone turnover
potentially driving tumor dissemination and priming the metastatic niche in bone. Further, using a FRET-based
Pi sensor we have observed marked differences in cytosolic Pi levels within individual lung cancer cells.
Suggesting that tumor cells have varying degrees to which they can sense and respond to changes in Pi levels.
Thus, leading to the postulation that a subpopulation of tumor cells is more sensitive to fluctuations in Pi and as
a result drive tumor progression and metastasis to the bone. Studies proposed herein will use a state-of-the-art
mouse metastasis model and a fluorescent Pi sensor to monitor Pi metabolism in real-time to examine the role
of phosphate availability in promoting lung cancer invasion and colonization of the bone. Specifically, we will test
the hypothesis that high Pi availability in lung cancer is pro-invasion and pro-metastatic, and specifically
influences the metastatic burden in the bone. Further, we will examine if heterogeneity in Pi transport within lung
cancer cell lines promotes tumor cell homing to bone. To test this hypothesis, we will: 1) Determine if serum
phosphate levels promote lung cancer invasion and bone metastasis and 2) Determine the cellular requirement
of phosphate for tumor invasion and metastasis to bone. Results from the current proposal will provide new
information about the role of Pi in altering cell behavior and mechanisms underlying tumor dissemination and
colonization of the skeleton.

## Key facts

- **NIH application ID:** 10145965
- **Project number:** 1F32CA257436-01
- **Recipient organization:** EMORY UNIVERSITY
- **Principal Investigator:** Jamie Arnst
- **Activity code:** F32 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2021
- **Award amount:** $79,386
- **Award type:** 1
- **Project period:** 2021-02-01 → 2024-01-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10145965

## Citation

> US National Institutes of Health, RePORTER application 10145965, Role of phosphate availability in lung cancer invasion and bone metastasis (1F32CA257436-01). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10145965. Licensed CC0.

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