patient-derived-orthotopic-xenograft-models-for-human-urothelial-cell

Patient-derived Orthotopic Xenograft Models for Human Urothelial Cell Carcinoma and Colorectal Cancer Tumor Growth and Spontaneous Metastasis

Cancer patients have poor prognoses when lymph node (LN) involvement is present in both high-grade urothelial cell carcinoma (HG-UCC) of the bladder and ...

In the United States, prostate cancer is the second most common cause of cancer-related deaths in men. While the importance of androgens and androgen receptors (ARs) in primary prostate cancer is well established, the role of ARs in prostate cancers that emerge despite androgen ablation therapies remains poorly understood. The aim of this article is to illustrate the fundamental biology of prostate cancer. We focus mainly on the AR because of its critical role in the progression and metastatic spread of prostate cancer. We also summarize the alternate pathways that may potentially contribute to the progression of prostate cancer. Identifying the underlying mechanisms of androgen independence is crucial in the design of appropriate therapies for hormone-refractory neoplasms.

Pathogenesis of prostate cancer: lessons from basic research.

Chicken sarcoma to human cancers: a lesson in molecular therapeutics.

High-grade urothelial cell carcinoma of the bladder has a poor prognosis when lymph nodes are involved. Despite curative therapy for clinically-localized disease, over half of the muscle-invasive urothelial cell carcinoma patients will develop metastases and die within 5 years. There are currently no described xenograft models that consistently mimic urothelial cell carcinoma metastasis. To develop a patient-derived orthotopic xenograft model to mimic clinical urothelial cell carcinoma progression to metastatic disease, the urothelial cell carcinoma cell line UM-UC-3 and two urothelial cell carcinoma patient specimens were doubly tagged with Luciferase/RFP and were intra-vesically (IB) instilled into NOD/SCID mice with or without lymph node stromal cells (HK cells). Mice were monitored weekly with bioluminescence imaging to assess tumor growth and metastasis. Primary tumors and organs were harvested for bioluminescence imaging, weight, and formalin-fixed for hematoxylin and eosin and immunohistochemistry staining. In this patient-derived orthotopic xenograft model, xenograft tumors showed better implantation rates than currently reported using other models. Xenograft tumors histologically resembled pre-implanted primary specimens from patients, presenting muscle-invasive growth patterns. In the presence of HK cells, tumor formation, tumor angiogenesis, and distant organ metastasis were significantly enhanced in both UM-UC-3 cells and patient-derived specimens. Thus, we established a unique, reproducible patient-derived orthotopic xenograft model using human high-grade urothelial cell carcinoma cells and lymph node stromal cells. It allows for investigating the mechanism involved in tumor formation and metastasis, and therefore it is useful for future testing the optimal sequence of conventional drugs or the efficacy of novel therapeutic drugs.

A patient-derived orthotopic xenograft model enabling human high-grade urothelial cell carcinoma of the bladder tumor implantation, growth, angiogenesis, and metastasis.

Article	Year
Pathogenesis of prostate cancer: lessons from basic research. The Ochsner journal\| PubMed ID: 21603505	2008
Chicken sarcoma to human cancers: a lesson in molecular therapeutics. The Ochsner journal\| PubMed ID: 21603517	2007
A patient-derived orthotopic xenograft model enabling human high-grade urothelial cell carcinoma of the bladder tumor implantation, growth, angiogenesis, and metastasis. Oncotarget\| PubMed ID: 30220977	2018

Stephen Bardot

Biography

JoVE Journal Publications

Other Publications