# Role of the smooth muscle layer in bladder cancer biology and progression: a systems and experimental approach

> **NIH NIH R21** · WEILL MEDICAL COLL OF CORNELL UNIV · 2022 · $374,052

## Abstract

PROJECT SUMMARY
Carcinomas are the most common cancers. In tumors arising in hollow organs, two major events
during tumor progression are disruption of the basement membrane and invasion of the smooth
muscle layer. In bladder cancer, muscle-invasion is associated with lymph node and distant
metastases and poor prognosis. Despite extensive interest in the tumor microenvironment, virtually
nothing is known about how tumor cells and smooth muscle cells (SMC) interact. Preliminary
observations support our central hypothesis that the smooth muscle layer may promote, rather than
restrain, tumor progression and that it can impact on the tumor cell phenotype in a context-
dependent manner. We aim to address this significant knowledge gap through a top-down systems
and bottom-up experimental approach. In Aim 1, we propose combining high-throughput and
spatially-resolved single cell expression profiling with innovative computational analyses of cell-cell
interactions in samples from patients with muscle-invasive bladder cancer to identify cellular
interactions that modulate tumor cell phenotype at the muscle-invasive front. Special emphasis will
be placed on interrogating tumor cell-SMC crosstalk at this interface, although all autocrine and
paracrine interactions will be analyzed at a systems level in an unbiased fashion. In Aim 2, we
propose using co-culture systems to mechanistically dissect tumor cell-SMC crosstalk, including
identifying transcriptomic changes induced by SMC on tumor cells, determining whether this cross-
talk is mediated by contact or soluble factors, and identifying candidate pathways that underlie this
effect for downstream validation. The amalgamation of these approaches will reveal markers of
SMC activation with prognostic and/or predictive value and may lead to the discovery of new
therapeutic targets for muscle-invasive bladder cancer. We expect to uncover a yet unexplored role
of the tumor microenvironment in bladder cancer phenotypes and progression.

## Key facts

- **NIH application ID:** 10527880
- **Project number:** 1R21CA266660-01A1
- **Recipient organization:** WEILL MEDICAL COLL OF CORNELL UNIV
- **Principal Investigator:** Ashley Marie Laughney
- **Activity code:** R21 (R01, R21, SBIR, etc.)
- **Funding institute:** NIH
- **Fiscal year:** 2022
- **Award amount:** $374,052
- **Award type:** 1
- **Project period:** 2022-09-12 → 2025-03-31

## Primary source

NIH RePORTER: https://reporter.nih.gov/project-details/10527880

## Citation

> US National Institutes of Health, RePORTER application 10527880, Role of the smooth muscle layer in bladder cancer biology and progression: a systems and experimental approach (1R21CA266660-01A1). Retrieved via AI Analytics 2026-05-24 from https://api.ai-analytics.org/grant/nih/10527880. Licensed CC0.

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