Establishment of a model of sentinel lymph node metastasis using immunodeficient swine

Abstract

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.

Features of the functioning of the natural defense mechanisms of piglets under the influence of immunotropic substances

“…few peripheral lymphoid cells, immature lymphoid tissues, and no effector and memory T-lymphocytes (Suzuki et al, 2014;Poonsuk & Zimmerman, 2018). Swine do not become fully immunologically competent until about 4 weeks of age, which means that their compromised ability to respond to infectious agents during the first month of life must be supplemented by maternal immune components: circulating antibodies derived from colostrum; mucosal antibodies from colostrum and milk; and immune cells provided in mammary secretions (Kurihara et al, 2019;Masiuk et al, 2022). Because maternal immunity is highly effective at protecting piglets against specific pathogens, strengthening sow herd immunity against certain diseases through exposure or vaccination is a useful management tool for ameliorating clinical effects in piglets and delaying infection until the piglets' immune system is better prepared to respond (Grześkowiak et al, 2020;Zheng et al, 2021).…”

Intraoperative laparoscopic detection of sentinel lymph nodes with indocyanine green and superparamagnetic iron oxide in a swine gallbladder cancer model

“…Swine provide an appropriate model for measuring lymphatic flow and are useful for visceral preclinical surgical simulations because their anatomy and size are similar to that of humans, and they have been widely used in endoscopic and surgical training [ 22 ]. In addition, we previously established a lymph node metastasis model of a subcutaneous tumour using recombination activating gene 2 (RAG2) -knockout (KO) immunodeficient swine [ 23 ] to evaluate the cancer-bearing circumstance that closely reflects the clinical situation.…”