The Regulation of Lymph Node Pre-Metastatic Niche Formation in Head and Neck Squamous Cell Carcinoma

Abstract

In many distinct forms of malignancies, there is a close relationship between lymph node (LN) metastases and further dissemination to distant organs, and this is a critical prognostic factor. At the beginning of the process, the original tumor secretes soluble substances or releases extracellular vesicles (EVs) that are carried through lymphatic channels to draining (sentinel) LN. The tumor-derived factors then drive LN remodeling. These significant alterations occur prior to the emergence of the first metastatic cell, bringing about the development of a pre-metastatic niche that allows metastatic cells to survive and thrive. In this review, we discuss current information available about the regulation of lymph node pre-metastatic niche in head and neck squamous cell carcinoma (HNSCC), and the role of EVs in forming the pre-metastatic niche.

Cancer-associated fibroblast-derived extracellular vesicles promote lymph node metastases in oral cavity squamous cell carcinoma by encapsulating ITGB1 and BMI1

“…CAF are accountable for increasing malignant features of head and neck cancer cells, and one of the many avenues taken by CAF to affect cancer cell behavior is the secretion of EVs with cargoes [ 13 ]. Lymph node metastases are common in many cancers and associated with unsatisfactory prognosis, and the formation of lymph node pre-metastatic niches is aided by the discharge of EVs [ 14 ]. Therefore, further investigation of the effect of EVs on lymph node metastases appears crucial.…”

circFNDC3B Accelerates Vasculature Formation and Metastasis in Oral Squamous Cell Carcinoma

“…LN metastasis, a major metastatic pattern of OSCC, is a multistep process involving epithelial–mesenchymal transition (EMT) and the intermediate state of EMT (p-EMT) associated with migration, invasion, and orchestrating the metastatic tumor microenvironment (TME) such as angiogenesis and lymphangiogenesis ( 5, 6 ). Of note is that lymphangiogenesis is a key determinant of metastatic progression and a promising predictor of patient outcomes ( 7 ). The prospero homeobox 1 (PROX1) and sex-determining region Y-box 18 (SOX18) transcription factors regulate the lymphangiogenic process by controlling the initiation of endothelial branching and spreading ( 8 ).…”

Evaluation of premetastatic changes in lymph nodes(pN0) of oral tongue tumour: A prospective observational Study

“…Their elevated levels are associated with LN and distant metastasis 4 , 5 . Several tyrosine kinase receptors are targeted by receptor tyrosine kinase inhibitors, however, the exact pathway is unknown 6 . The S1PR1-STAT3 pathway enables myeloid cells to intravasate, turning the organ microenvironment conducive for proliferation, survival, and initiation of metastasis 7 .…”

“…Several growth hormones, RNA, cytoplasmic proteins, and growth factors like Periostin, VEGF, Angiopoietins, Laminin γ2, and Insulin-like growth factor (IGF)-1/2 which are involved in the induction of lymphangiogenesis. Moreover the activation of mTOR, podoplanin, and lymphatic vessel endothelial hyaluronan receptor 1(LYVE-1), extracellular vesicle, and HPV +ve tumors may affect the lymphangiogenesis 6 .…”