Establishment of an orthotopic prostate cancer xenograft mouse model using microscope-guided orthotopic injection of LNCaP cells into the dorsal lobe of the mouse prostate

Weiyong Liu,Lei Ye,Yuhao Wang,Yajuan Zhu,Yunkai Zhu

doi:10.1186/s12885-022-09266-0

Abstract

BackgroundOrthotopic LNCaP xenograft mouse models closely mimic the progression of androgen-dependent prostate cancer in humans; however, orthotopic injection of LNCaP cells into the mouse prostate remains a challenge.MethodsUnder the guidance of a stereoscopic microscope, the anatomy of the individual prostate lobes in male Balb/c athymic nude mice was investigated, and LNCaP cells were inoculated into the mouse dorsal prostate (DP) to generate orthotopic tumors that mimicked the pathophysiological process of prostate cancer in humans. Real-time ultrasound imaging was used to monitor orthotopic prostate tumorigenesis, contrast-enhanced ultrasonography (CEUS) was used to characterize tumor angiogenesis, and macroscopic and microscopic characteristics of tumors were described.ResultsThe DP had a trigonal bipyramid-shape and were located at the base of the seminal vesicles. After orthotopic inoculation, gray scale ultrasound imaging showed progressive changes in tumor echotexture, shape and location, and tumors tended to protrude into the bladder. After 8 weeks, the tumor take rate was 65% (n = 13/20 mice). On CEUS, signal intensity increased rapidly, peaked, and decreased gradually. Observations of gross specimens showed orthotopic prostate tumors were well circumscribed, round, dark brown, and soft, with a smooth outer surface and a glossy appearance. Microscopically, tumor cells were arranged in acini encircled by fibrous septa with variably thickened walls, mimicking human adenocarcinoma.ConclusionsThis study describes a successful approach to establishing an orthotopic LNCaP xenograft Balb/c athymic nude mouse model. The model requires a thorough understanding of mouse prostate anatomy and proper technique. The model represents a valuable tool for the in vivo study of the biological processes involved in angiogenesis in prostate cancer and preclinical evaluations of novel anti-angiogenic therapies.

Highlights

Orthotopic LNCaP xenograft mouse models closely mimic the progression of androgen-dependent prostate cancer in humans; orthotopic injection of LNCaP cells into the mouse prostate remains a challenge
Under the guidance of a stereoscopic microscope, we investigated the anatomy of the individual prostate lobes in male Balb/c athymic nude mice and inoculated LNCaP cells into the mouse dorsal prostate (DP) to generate orthotopic tumors that mimicked the pathophysiological process of prostate cancer in humans
The bilateral lateral prostate (LP) appeared as cerebriform structures with a slightly inverted trapezium-like shape

Summary

Introduction

Orthotopic LNCaP xenograft mouse models closely mimic the progression of androgen-dependent prostate cancer in humans; orthotopic injection of LNCaP cells into the mouse prostate remains a challenge. Animal models that mimic the natural history of prostate cancer in humans are required to improve our understanding of disease progression. The LNCaP cell line constitutes androgen receptorpositive prostate cancer cells that express prostatespecific antigen (PSA) and prostate specific membrane antigen (PSMA), a marker of disease aggressiveness [3]. Subcutaneous and orthotopic LNCaP xenograft animal models closely mimic the progression of androgendependent prostate cancer in humans. The development of reproducible orthotopic prostate cancer xenografts is more demanding than a subcutaneous procedure. The inoculation of orthotopic tumors in the prostate of nude mice is technically challenging, and the take rate of LNCaP cells is low, even with the addition of Matrigel [5]

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