A reliable murine model of bone metastasis by injecting cancer cells through caudal arteries

Takahiro Kuchimaru,Tatsuhiro Isozaki,Tetsuya Kadonosono,Shinae Kizaka-Kondoh,Misa Minegishi,Kenji Nakagawa,Naoya Kataoka,Hitomi Miyabara

doi:10.1038/s41467-018-05366-3

Takahiro Kuchimaru, Tatsuhiro Isozaki + Show 6 more

Open Access

https://doi.org/10.1038/s41467-018-05366-3

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Journal: Nature Communications	Publication Date: Jul 30, 2018
Citations: 86	License type: open-access

Affiliation: Tokyo Institute of Technology

Abstract

Although the current murine model of bone metastasis using intracardiac (IC) injection successfully recapitulates the process of bone metastasis, further progress in the study of bone metastasis requires a new model to circumvent some limitations of this model. Here, we present a new murine model of bone metastasis achieved by injecting cancer cells through the intra-caudal arterial (CA). This model does not require high technical proficiency, predominantly delivers cancer cells to bone marrow of hind limbs with much higher efficiency than IC injection, and greatly shortens the period of overt bone metastasis development. Moreover, CA injection barely causes acute death of mice, enabling us to inject a larger number of cancer cells to further accelerate the development of bone metastasis with a wide variety of cell lines. Our model may open a new avenue for understanding the bone metastatic processes and development of drugs preventing bone metastasis and recurrence.

Highlights

The current murine model of bone metastasis using intracardiac (IC) injection successfully recapitulates the process of bone metastasis, further progress in the study of bone metastasis requires a new model to circumvent some limitations of this model
Because the nanoparticles injected via caudal arterial (CA) were thought to eventually travel to the tail vein, we compared their distributions after CA and intravenous (IV) injection by video-rate fluorescence imaging
CAinjection exhibited totally different routes from IV injection: Injecting nanoparticles into the CA quickly illuminated the capillary bed in the lower body of mice, whereas nanoparticles injected via the tail vein resulted in slow and modest illumination (Fig. 1b and Supplementary Movies 1 and 2)

Summary

Introduction

The current murine model of bone metastasis using intracardiac (IC) injection successfully recapitulates the process of bone metastasis, further progress in the study of bone metastasis requires a new model to circumvent some limitations of this model. We present a new murine model of bone metastasis achieved by injecting cancer cells through the intra-caudal arterial (CA) This model does not require high technical proficiency, predominantly delivers cancer cells to bone marrow of hind limbs with much higher efficiency than IC injection, and greatly shortens the period of overt bone metastasis development. IC injection, is insufficient for rapid studies in this field, mainly owing to its requirement for high technical proficiency to exactly insert a syringe needle into the left ventricle of a mouse, causing severe cardiac stresses[3,4] This limits the number of cancer cells that can be injected at one time, leading to limited delivery of cancer cells to the bone. CA injection provides an easy-to-use murine model to develop overt bone metastasis in a short time and could greatly facilitate studies to understand bone metastasis and to prevent them

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