Abstract 385: Stress-induced pentraxin 3 enhances anoikis resistant-associated metastasis and post-chemotherapeutic recurrence in head and neck cancer

Abstract

Abstract Head and neck squamous cell carcinoma (HNSCC) is one of the most aggressive cancer with the properties of local recurrence and lymphatic metastasis. During metastatic process in blood circulation, cancer cells lose the interaction with extracellular matrix and encounter the anoikis stress, resulting in successfully extravasate and form micrometastasis in distal organs. However, most patients develop chemo-drug resistance during the metastatic recurrence which leading to poor prognosis. Thus, it is a pressing matter to elucidate the molecular mechanisms involved in cancer metastasis and the behaviors of the post-chemotherapy treated HNSCC cells. Our previous studies suggest that growth factor signaling stimulated HNSCC cells metastasis by the expression of pentraxin 3 (PTX3). Moreover, recent findings also reveal that chemotherapy mediated oxidative stress induce PTX3 expression and poor progression. Here, we raise the hypothesis that the expression of PTX3 through stress signal may promote cancer cells against from anoikis and promote the post-chemotherapeutic survival. The first, we identified that the secondary messenger-reactive oxygen species (ROS) dominate the gene activation of PTX3 by spheroid culture and platium-based agents’ treatment. The ROS scavenger, NAC, inhibited cisplatin (CDDP)-induced PTX3 expression and rescue the cell viability by decreasing the ROS level. The oxidative stress inducer-H2O2 treatment also verify the PTX3 expression through AKT and NF-κB pathways. In addition, both the spheroid selection and CDDP-induced PTX3 regulated the EMT phenotype and further strengthen the growth factor signaling. In addition, we found that PTX3 also regulate the survival during spheroid selection and drug treatment. The post-selected cells also exhibit the unique glycosylated modification on PTX3. Disrupted the PTM modification of PTX3 could inhibit the spheroid survival and cell invasion. The animal studies revealed that both spheroid selection and CDDP-treated HNSCC cells had stronger extravasation ability than parental cells in NOD-SCID mice. Depletion of PTX3 also repressed the HNSCC cells extravasation ability. The results indicate that PTX3 were essential for oxidative stress-induced tumor metastasis and recurrence. It also speculates that the combination of antioxidants and PTX3 antibody may prevent tumor metastatic recurrence after chemotherapy in HNSCC. Citation Format: Ting-Wei Chang, Wen-Chang Chang, Ben-Kuen Chen. Stress-induced pentraxin 3 enhances anoikis resistant-associated metastasis and post-chemotherapeutic recurrence in head and neck cancer [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 385.