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会議情報: 大気球シンポジウム 平成18年度（2007年1月15-16日. 宇宙航空研究開発機構宇宙科学研究本部 (JAXA)(ISAS)）, 相模原市, 神奈川県), 著者人数: 22名, Meeting Information: Balloon Symposium 2006 (January 15-16, 2007. Institute of Space and Astronautical Science, Japan Aerospace Exploration Agency (JAXA)(ISAS)), Sagamihara, Kanagawa Japan

The version of record of this article, first published in Clinical and Experimental Metastasis, is available online at Publisher’s website: https://doi.org/10.1007/s10585-024-10306-1., The process of cervical lymph node metastasis is dependent on the phenotype of the tumor cells and their interaction with the host microenvironment and immune system; conventional research methods that focus exclusively on tumor cells are limited in their ability to elucidate the metastatic mechanism. In cancer tissues, a specialized environment called the tumor microenvironment (TME) is established around tumor cells, and inflammation in the TME has been reported to be closely associated with the development and progression of many types of cancer and with the response to anticancer therapy. In this study, to elucidate the mechanism of metastasis establishment, including the TME, in the cervical lymph node metastasis of oral cancer, we established a mouse-derived oral squamous cell carcinoma cervical lymph node highly metastatic cell line and generated a syngeneic orthotopic transplantation mouse model. In the established highly metastatic cells, epithelial-mesenchymal transition (EMT) induction was enhanced compared to that in parental cells. In the syngeneic mouse model, lymph node metastasis was observed more frequently in tumors of highly metastatic cells than in parental cells, and Cyclooxygenase-2 (COX-2) expression and lymphatic vessels in primary tumor tissues were increased, suggesting that this model is highly useful. Moreover, in the established highly metastatic cells, EMT induction was enhanced compared to that in the parent cell line, and CCL5 and IL-6 secreted during inflammation further enhanced EMT induction in cancer cells. This suggests the possibility of a synergistic effect between EMT induction and inflammation. This model, which allows for the use of two types of cells with different metastatic and tumor growth potentials, is very useful for oral cancer research involving the interaction between cancer cells and the TME in tumor tissues and for further searching for new therapeutic agents.

Nishimura J., Morita Y., Tobe-Nishimoto A., et al. CDDP-induced desmoplasia-like changes in oral cancer tissues are related to SASP-related factors induced by the senescence of cancer cells. International Immunopharmacology 136, 112377 (2024); https://doi.org/10.1016/j.intimp.2024.112377., The tumor microenvironment (TME) concept has been proposed and is currently being actively studied. The development of extracellular matrix (ECM) in the TME is known as desmoplasia and is observed in many solid tumors. It has also been strongly associated with poor prognosis and resistance to drug therapy. Recently, cellular senescence has gained attention as an effect of drug therapy on cancer cells. Cellular senescence is a phenomenon wherein proliferating cells become resistant to growth-promoting stimuli, secrete the SASP (senescence-associated phenotypic) factors, and stably arrest the cell cycle. These proteins are rich in pro-inflammatory factors, such as interleukin (IL)-6, IL-8, C-X-C motif chemokine ligand 1, C–C motif chemokine ligand (CCL)2, CCL5, and matrix metalloproteinase 3. This study aimed to investigate the desmoplasia-like changes in the TME before and after cancer drug therapy in oral squamous cell carcinomas, evaluate the effect of anticancer drugs on the TME, and the potential involvement of cancer cell senescence. Using a syngeneic oral cancer transplant mouse model, we confirmed that cis-diamminedichloroplatinum (II) (CDDP) administration caused desmoplasia-like changes in cancer tissues. Furthermore, CDDP treatment-induced senescence in tumor-bearing mouse tumor tissues and cultured cancer cells. These results suggest CDDP administration-induced desmoplasia-like structural changes in the TME are related to cellular senescence. Our findings suggest that the administration of anticancer drugs alters the TME of oral cancer cells. Additionally, oral cancer cells undergo senescence, which may influence the TME through the production of SASP factors.