Abstract
Abstract Due to genetically unstable nature of cancer cells, they give rise to genetically different variant subclones inside a single tumor. To enable the development of more efficacious therapies, it is crucial to understand cancer heterogeneity and subclone characteristics. Oral squamous cell carcinoma (OSCC) has high heterogeneity and plasticity. C-X3-C motif ligand 1 (CX3CL1) is the chemokine with anti- and pro-tumor functions. Our study reported CX3CL1 functions on cancer subclones with different phenotypes, both in vivo and in vitro. We found that Mouse OSCC (MOC) 1 and MOC2 cells responded in similar manners to CX3CL1 in vitro. However, in vivo, CX3CL1 increases cellular differentiation in indolent cancer (MOC1) while increasing metastasis in aggressive cancer (MOC2). These phenomena are influenced by different phenotypic tumor microenvironments created by indolent and aggressive cancer. From there, we established that when aggressive cancer cells gain CX3CL1 expression, they stimulate protumor immune system, promoting cancer metastasis via lymphatic vessels. A similar phenomenon was observed in metastatic OSCC patient samples, where CX3CL1 expression became intense in metastasis regions, consistent with aggressive subclone (MOC2) character; we correctly predicted patient outcomes by using CX3CL1 as prognostic indicator for long-term follow-up in metastatic OSCC patients. In conclusion, CX3CL1 is the key factor for stimulating aggressive cancer subclones to create new lymphatic networks for lymph node metastasis. Citation Format: Hotaka Kawai, Htoo Shwe Eain, Toshiaki Ohara, May Wathone Oo, Yamin So, Hitoshi Nagatsuka. Oral squamous carcinoma, LN metastasis [abstract]. In: Proceedings of the American Association for Cancer Research Annual Meeting 2024; Part 1 (Regular Abstracts); 2024 Apr 5-10; San Diego, CA. Philadelphia (PA): AACR; Cancer Res 2024;84(6_Suppl):Abstract nr 3783.
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