Abstract
Animal studies of lymph node metastasis are constrained by limitations in the techniques available for noninvasive monitoring of the progression of lymph node metastasis, as well as difficulties in the establishment of appropriate animal models. To overcome these challenges, this study has developed a mouse model of inter-lymph-node metastasis via afferent lymphatic vessels for use in the development of imaging modalities. We used 14- to 18-week-old MRL/MpJ−/lpr/lpr (MRL/lpr) mice exhibiting remarkable systemic lymphadenopathy, with proper axillary lymph nodes (proper-ALNs) and subiliac lymph nodes (SiLNs) that are 6 to 12 mm in diameter (similar in size to human lymph nodes). When KM-Luc/GFP malignant fibrous histiocytoma-like cells stably expressing the firefly luciferase gene were injected into the SiLN, metastasis could be detected in the proper-ALN within 3 to 9 days, using in vivo bioluminescence imaging. The metastasis route was found to be via the efferent lymphatic vessels of the SiLN, and metastasis incidence depended on the number of cells injected, the injection duration and the SiLN volume. Three-dimensional contrast-enhanced high-frequency ultrasound imaging showed that the blood vessel volume and density in the metastasized proper-ALN significantly increased at 14 days after tumor cell inoculation into the SiLN. The present metastasis model, with lymph nodes similar in size to those of humans, has potential use in the development of ultrasound imaging with high-precision and high-sensitivity as well as other imaging modalities for the detection of blood vessels in lymph nodes during the progression of metastasis.
Highlights
Human lymph nodes are round or kidney-shaped organs of the immune system, 2 to 20 mm in diameter, that are distributed throughout the body [1,2]
ALN, indocyanine green (ICG) was injected into the subiliac lymph nodes (SiLNs) at 0.5 to 3.0 mL/h, and the flow was observed with the in vivo bioluminescence imaging system (IVIS) (Fig. 1A) and photodynamic camera (PDE) (Fig. 1B)
To determine whether metastasis had occurred via the veins or the afferent lymphatic vessels, FITC solution was injected into the SiLN and the flow observed using high-speed fluorescence video camera system (HS-FVCS) (Fig. 1D)
Summary
Human lymph nodes are round or kidney-shaped organs of the immune system, 2 to 20 mm in diameter, that are distributed throughout the body [1,2]. The two major transplantation models of metastasis currently used are referred to as the spontaneous and the experimental metastasis models [8] In the former model, tumor cells are injected into an anatomic location (orthotopic implantation), in the tissue from which the tumor had been derived (orthotopic implantation) or in subcutaneous tissue (heterotopic implantation) [8]. In the latter model, tumor cells are directly injected into the circulation (e.g., into the spleen, tail vein or left cardiac ventricle), offering an attractive platform for the study of diagnostic imaging and treatment monitoring [9,10]. Most lymph node metastasis models are based on the spontaneous metastasis model [11], and these have provided valuable information concerning the biology of lymphatic metastasis [12,13], lymphatic architecture mapping [14,15], tumor-cell shedding and trafficking in lymphatic channels [16], and sentinel lymph node mapping [6,17,18]
Sign-in/Register to view highlights & summary Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
