TSD Program Seminar: Nadia Lanman

Nadia Lanman and Bennett Elzey, research associate professors at the Purdue Institute for Cancer Research, will be speakers for the Targets, Structures and Drugs (TSD) Scientific Program event series.

Seminar Title: Developing Cross-Species Models to Study Metastasis in Invasive Urothelial Carcinoma

Invasive urothelial carcinoma (InvUC) is a highly lethal disease, with over 50% of patients developing distant metastases that are nearly always fatal. The biological processes driving metastasis remain poorly understood, limiting our ability to predict or prevent progression. Naturally occurring canine InvUC closely mirrors the human disease in presentation, pathology, molecular subtypes and metastatic behavior, offering a powerful comparative oncology model for studying the metastatic cascade.

This study aimed to (1) determine whether circulating tumor cells (CTCs) can be detected via flow cytometry, (2) define the optimal window for CTC detection and (3) identify canine models suitable for studying InvUC metastasis. We characterized low-passage canine InvUC cell lines representing basal (AXC, AN) and luminal (AXA, SH) subtypes using in vitro and in vivo approaches. Basal AXC and AN cell lines were highly invasive. Non-resected tumors grown to endpoint developed few grossly detectable metastases, whereas resection of smaller tumors consistently revealed visible metastases.

The basal AXC line yielded the highest CTC counts among all tested lines, and larger tumor burden correlated with higher CTC counts overall. Resection triggered a transient CTC spike, but unresected tumors ultimately yielded more CTCs. We also developed PDX models from a canine lymph node metastasis and a primary bladder tumor. The lymph node-derived PDX metastasized most extensively — to the lungs, spleen, diaphragm and kidneys — yet paradoxically produced the fewest CTCs of any model, while the bladder-derived PDX showed more limited spread.

To complement these models molecularly, we analyzed single-cell RNA-sequencing data from 17 dogs with InvUC, resolving major cellular compartments and identifying differentially expressed genes associated with metastasis. Together, these findings establish canine cell line, PDX and single-cell transcriptomic resources spanning a range of metastatic potential, revealing an unexpected dissociation between metastatic burden and CTC shedding and candidate genes warranting further investigation.