# An organ-on-a-chip model system to study prostate cancer metastasis into vascularized bone

> **NIH NIH R21** · OREGON HEALTH & SCIENCE UNIVERSITY · 2022 · $215,985

## Abstract

PROJECT SUMMARY
Based on “seed and soil” theory, certain tumors exhibit a predilection for metastasis to particular organs. For
example, bone is the most common site of metastasis for prostate cancer, happening in ~90% of patients with
advanced stages of prostate cancer. Organ-on-a-chip models of cancer metastasis have emerged as a powerful
predictor of cancer progression. However, despite the development in organ-on-a-chip platforms for in-vitro
studies in metastasis, research in bone metastasis on-a-chip remains largely underdeveloped, and the only few
available models in the literature lack the complex mineralization and the inclusion of bone cells, especially
osteoclasts into the system, which are essential elements in order to study bone remodeling. Here, (aim 1) we
will use a novel organ-on-a-chip platform with a highly mineralized and calcified cell-laden hydrogel including
osteoclasts to determine the influence of mineralization and the cross-talk of prostate cancer cells and bone cells
on the process of preferential prostate cancer growth in bone and the consequent bone resorption. A potentially
rate-limiting step in metastasis formation is the extravasation process that involves adhesion of tumor cells to
endothelial cells and their transmigration through the endothelial cell monolayer and basement membrane. It has
been well-established that pericyte-support of EC capillaries is required for formation of non-leaky vessels and
perturbation of the EC-hMSC linkage, therefore results in leaky vessels. The role of pericytes in tumor metastasis
has been mostly focused on tumor angiogenesis and the research on the role of this cell type on cancer
extravasation has remained underdeveloped. Here, (aim 2) we will use the bone metastasis-on-a-chip platform
to test the role of pericytes in a vasculature embedded in a mineralized bone matrix in inhibiting human prostate
cancer extravasation as well as the effects of factors released by cancer cells on vasculature integrity. We argue
that this multi-pronged strategy will enable the engineering of in-vitro bone metastasis-on-a-chip model system
to understand the preferential metastasis of prostate cancer to the bone and bone destruction as well as the role
of pericytes in prostate cancer extravasation through the vasculature. Ultimately, this project will lead to model
systems that can be used for studying cancer metastasis to bone and developing new treatments.

## Key facts

- **NIH application ID:** 10373347
- **Project number:** 1R21CA263860-01A1
- **Recipient organization:** OREGON HEALTH & SCIENCE UNIVERSITY
- **Principal Investigator:** Luiz Eduardo Bertassoni
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $215,985
- **Award type:** 1
- **Project period:** 2021-12-31 → 2023-11-30

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10373347

## Citation

> US National Institutes of Health, RePORTER application 10373347, An organ-on-a-chip model system to study prostate cancer metastasis into vascularized bone (1R21CA263860-01A1). Retrieved via AI Analytics 2026-05-23 from https://api.ai-analytics.org/grant/nih/10373347. Licensed CC0.

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