What question did this study set out to answer?

Identify the role of COL2A1 in Wilms tumor progression and its potential as a therapeutic target.

April 5, 2026

Abstract 7478: Targeting the extracellular matrix in Wilms tumor

Key Points

Identify the role of COL2A1 in Wilms tumor progression and its potential as a therapeutic target.
Profiled Wilms tumor using cancer stem cell-like progenitors and patient-derived xenografts.
Conducted comparative transcriptomics on cancer stem cells cultured on decellularized ECM.
Performed functional assays to assess effects of COL2A1 inhibition on EMT and chemotherapy response.
COL2A1-enriched environments activated AKT signaling and induced EMT.
Blocking COL2A1 reversed EMT markers and restored tumor suppressor expression.
Transcriptomic analysis correlated COL2A1 upregulation with increased tumorigenic pathways and reduced drug sensitivity.

Abstract

Abstract Introduction: Wilms tumor (WT) represents approximately 90% of pediatric renal malignancies. While standard treatments are effective for many patients, those with relapse or unfavorable histopathology experience poor survival and severe long-term toxicities. The extracellular matrix (ECM) plays a critical role in driving cancer progression and drug resistance. Our comprehensive profiling of WT revealed type II collagen alpha 1 (COL2A1), absent in normal kidney, to be highly expressed in high-risk tumors, highlighting its potential as a novel biomarker and therapeutic target. Methods: We utilized WT cancer stem cell (CSC)-like progenitors, 3D cultures, and patient-derived xenografts (PDXs) with metastatic and chemoresistant phenotypes to investigate COL2A1-mediated signaling. Comparative transcriptomics were performed on WT CSCs cultured on WT-versus normal kidney-derived decellularized ECM. Functional assays assessed epithelial-mesenchymal transition (EMT), tumor suppressor expression, and chemotherapy response following COL2A1 inhibition. Results: COL2A1-enriched substrates activated AKT signaling, induced EMT, downregulated tumor suppressors, and promoted chemoresistance. Transcriptomic analysis revealed COL2A1 upregulation alongside its transcriptional regulator SP1, correlating with enhanced tumorigenic pathways and reduced drug sensitivity. Notably, COL2A1 blockade using a specific antibody reversed EMT (i.e., increased cytokeratin and decreased vimentin), restored tumor suppressor expression, and enhanced chemotherapy response. Conclusions: COL2A1 is a critical ECM component driving therapy resistance in WT. Targeting COL2A1 offers a promising ECM-directed strategy to overcome treatment resistance and improve outcomes in high-risk WT patients. These findings highlight ECM-directed interventions as a new frontier in the treatment of pediatric kidney cancer. Citation Format: Wilson Yeung, Hripsime Chomoyan, Matthew E. Thornton, David S. Koos, Valentina Villani, Justin Sunwoo, Brendan H. Grubbs, Roger E. De Filippo, Laura Perin, Astgik Petrosyan. Targeting the extracellular matrix in Wilms tumor abstract. In: Proceedings of the American Association for Cancer Research Annual Meeting 2026; Part 1 (Regular Abstracts); 2026 Apr 17-22; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2026;86(7 Suppl):Abstract nr 7478.

Mark Helpful

Bookmark

Relay