TY - JOUR
T1 - Establishment of a model of sentinel lymph node metastasis using immunodeficient swine
AU - Kurihara, Toshiaki
AU - Matsuda, Sachiko
AU - Nakamura, Yuki
AU - Suzuki, Shunichi
AU - Fuchimoto, Daiichiro
AU - Onishi, Akira
AU - Saeki, Kohei
AU - Nakagawa, Takayuki
AU - Fujiwara, Reina
AU - Kamata, Masatoshi
AU - Kuramoto, Junko
AU - Kameyama, Kaori
AU - Sekino, Masaki
AU - Kusakabe, Moriaki
AU - Hayashida, Tetsu
AU - Jinno, Hiromitsu
AU - Kitagawa, Yuko
N1 - Funding Information:
Dr. Fumihiko Ishikawa (RIKEN Center for Integrative Medical Sciences, Kanagawa, Japan) and the staff of Prime Tech Ltd. (Tsuchiura, Ibaraki, Japan) contributed to the generation of RAG2-knockout swine. Dr Masayuki Yoshida (a pathologist at the National Cancer Center Hospital, Tokyo, Japan) assisted the evaluation of histological analyses. We thank Professor David Heery (University of Nottingham, Nottingham, UK) and Sumiko Matsuda for their support. We thank the Collaborative Research Resources Department, School of Medicine, Keio University for technical assistance. We thank Edanz Group (www.edanzediting.com/ac) for editing a draft of this manuscript. This study was supported by the Project for Medical Device Development from the Japan Agency for Medical Research and Development (AMED) under Grant Number JP18he0902010h0004.
Publisher Copyright:
© 2019, The Author(s).
PY - 2019/12/1
Y1 - 2019/12/1
N2 - Lymph node metastasis occurs via the migration of cancer cells through the lymphatic system. Sentinel lymph node (SLN) biopsy is a common diagnostic strategy. SLNs have been studied using healthy rodents and large animals without metastasis. Here we used immunodeficient swine to establish a model of lymph node metastasis. We used RAG2-knockout immunodeficient swine. A431 human epithelial carcinoma cells expressing green fluorescent protein were injected subcutaneously into the posterior sides of the auricle, forelimb and hindlimb of knockout swine. Indigo carmine dye was injected subcutaneously 8 weeks after tumour cell transplantation. SLNs were extracted, observed using a stereoscopic fluorescence microscope and analysed histologically using haematoxylin and eosin staining, and immunohistochemistry. Lymphoid follicles were found in wild-type swine, and a few aggregated lymphocytes and immature lymphoid follicles were observed in knockout swine. Fluorescence in the lymph nodes indicated metastasis of tumour cells to the lymph nodes. Tumour cells replaced lymph node architectures, showed high-grade nuclear atypia and formed irregular tumour nests. Our model may be useful for the preclinical validation of diagnostic methods and minimally invasive treatment of metastatic cancer.
AB - Lymph node metastasis occurs via the migration of cancer cells through the lymphatic system. Sentinel lymph node (SLN) biopsy is a common diagnostic strategy. SLNs have been studied using healthy rodents and large animals without metastasis. Here we used immunodeficient swine to establish a model of lymph node metastasis. We used RAG2-knockout immunodeficient swine. A431 human epithelial carcinoma cells expressing green fluorescent protein were injected subcutaneously into the posterior sides of the auricle, forelimb and hindlimb of knockout swine. Indigo carmine dye was injected subcutaneously 8 weeks after tumour cell transplantation. SLNs were extracted, observed using a stereoscopic fluorescence microscope and analysed histologically using haematoxylin and eosin staining, and immunohistochemistry. Lymphoid follicles were found in wild-type swine, and a few aggregated lymphocytes and immature lymphoid follicles were observed in knockout swine. Fluorescence in the lymph nodes indicated metastasis of tumour cells to the lymph nodes. Tumour cells replaced lymph node architectures, showed high-grade nuclear atypia and formed irregular tumour nests. Our model may be useful for the preclinical validation of diagnostic methods and minimally invasive treatment of metastatic cancer.
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U2 - 10.1038/s41598-019-44171-w
DO - 10.1038/s41598-019-44171-w
M3 - Article
C2 - 31138877
AN - SCOPUS:85067289523
SN - 2045-2322
VL - 9
JO - Scientific reports
JF - Scientific reports
IS - 1
M1 - 7923
ER -
