Sentinel Lymph Node–Targeted Therapy by Oncolytic Sendai Virus Suppresses Micrometastasis of Head and Neck Squamous Cell Carcinoma in an Orthotopic Nude Mouse Model

Abstract

In clinical N0 (cN0) cases with head and neck squamous cell carcinoma (HNSCC), a treatment selection is still controversial: elective neck dissection or watchful waiting. We focused on sentinel lymph node (SLN)-targeted therapy using the urokinase-type plasminogen activator (uPA)dependent oncolytic Sendai virus "BioKnife." The objectives of this study were to investigate BioKnife migration into SLNs and elucidate its antitumor effect on lymph node metastases (LNM). We established an orthotopic nude mouse model of HNSCC, with LNM being frequently induced. We inoculated HSC-3-M3, human highly metastatic tongue squamous cell carcinoma cells, in the tongue of the nude mice, and after 2 weeks, we injected BioKnife into the primary tumor. We tracked BioKnife migration into the SLNs by immunostaining, RT-PCR, and an in vivo imag-ing system. We also examined its antitumor effects and mechanisms through serial section analysis of lymph nodes. GFP reporter expression was clearly visible in the lymph nodes of virus groups, which corresponded to SLNs. Relative GFP mRNA was significantly increased in both the tongues and lymph nodes in the virus groups compared with that in the control group (P < 0.05). Serial section analysis showed that BioKnife infected cancer cells and exhibited significant antitumor effect against LNM compared with the control groups (P < 0.05). We detected apoptosis in LNM infected by BioKnife. BioKnife migrated into SLNs after its injection into the primary tumor and effectively suppressed LNM, suggesting that SLN-targeted therapy using BioKnife has great potential to provide a novel and promising alternative to elective neck dissection in cN0 patients with HNSCC.

Transcriptomic Profiling Predicts Multiple Pathways and Molecules Associated With the Metastatic Phenotype of Oral Cancer Cells

“…When injected into the tongues of nude mice, HSC-3-M3 cells metastasize to cervical lymph nodes with a frequency of 90%, an incidence that is three times higher than that of parental HSC-3 cells (15). Although HSC-3-M3 cells have been used as a highly metastatic cell line model in a few articles (23,24), to date, none have reported on the differences in mRNA transcriptome with parental HSC-3 cells. We hypothesized that comparing the transcriptome between HSC-3 and HSC-3-M3 cells would reveal specific intracellular pathways, gene-regulatory networks, and key molecules associated with OSCC metastasis.…”

Sensitive Spatiotemporal Tracking of Spontaneous Metastasis in Deep Tissues via a Genetically-Encoded Magnetic Resonance Imaging Reporter

“…In fact, promotion of metastasis by antitumor therapies has been previously demonstrated in several major studies [46][47][48] . And on the opposite end, it may be that successful treatments for metastasis have been wrongly deemed ineffective simply because larger lesions dominated measurements 49 . Yet, above all, it is concerning that little emphasis has been placed on the discovery of antimetastatic therapies at the preclinical stage because the threshold of metastatic prevention and/or regression is extremely challenging to demonstrate with currently available technologies 50,51 .…”

Anlotinib Suppresses Oral Squamous Cell Carcinoma Growth and Metastasis by Targeting the RAS Protein to Inhibit the PI3K/Akt Signalling Pathway

“…Anlotinib is a novel small-molecule multitarget tyrosine kinase receptor inhibitor that is popular due to its anticancer properties and new side effects [ 5 , 6 ]. In a recent study, anlotinib mainly inhibited angiogenesis and tissue tumour cell migration by inhibiting c-Kit, VEGFR2, VEGFR3, FGFR1-4, PDGFR α and β , and other targets, thus inhibiting tumour [ 7 , 8 ].…”