IADR Abstract Archives
Oral cancer stimulated TNFα production and phenotypic transformation in macrophages
Objectives: Background: The initial stages of cancer development are recognised by immune cells such as M1 type macrophages. During tumour development macrophages become tolerant (M2) to the cancer cells and provide an environment for tumour growth. The mechanism of phenotypic switch from M1 to M2 type during tumorigenesis is not known.
Aims & Objective: The purpose of this study was to investigate the initial response of macrophages to head and neck squamous cell carcinoma (HNSCC) cells in vitro and to identify the molecular and cellular mechanisms that induce macrophage phenotype from M1 to M2.
Methods: 2D and 3D models using human macrophage cell line (THP-1) with head & neck squamous carcinoma cell lines (HNSCC) and their conditional medium were used. In some experiments, co-culture THP-1 cells were collected and further stimulated with LPS. Cytokine production was examined by ELISA and RT-qPCR. Cell aggregation and migration was assessed using time lapse microscope.
Results: 1) TNFα was transiently produced at 24hrs co-culture and reduced within 48hrs, partially due to the TNFα use by HNSCC cells. 2) Macrophage adherence and migration toward HNSCC occurred immediately after co-culture, but not observed in controls (osteosarcoma cell line MG63). 3) Degrees of cell aggregation were diverse between cell lines; however, macrophage aggregation was not associated with levels of TNFα production. 4) Following prolonged culture of THP-1 with HNSCC, THP-1 lost the ability to produce TNFα in response to LPS stimulation.
Conclusions: HNSCC produce soluble and membrane bound proteins that induce TNFα production in macrophages, which convert macrophages into a tolerogenic phenotype. Blocking the tolerogenic pathway could be a novel therapeutic method to limit the progression of oral cancer.
Aims & Objective: The purpose of this study was to investigate the initial response of macrophages to head and neck squamous cell carcinoma (HNSCC) cells in vitro and to identify the molecular and cellular mechanisms that induce macrophage phenotype from M1 to M2.
Methods: 2D and 3D models using human macrophage cell line (THP-1) with head & neck squamous carcinoma cell lines (HNSCC) and their conditional medium were used. In some experiments, co-culture THP-1 cells were collected and further stimulated with LPS. Cytokine production was examined by ELISA and RT-qPCR. Cell aggregation and migration was assessed using time lapse microscope.
Results: 1) TNFα was transiently produced at 24hrs co-culture and reduced within 48hrs, partially due to the TNFα use by HNSCC cells. 2) Macrophage adherence and migration toward HNSCC occurred immediately after co-culture, but not observed in controls (osteosarcoma cell line MG63). 3) Degrees of cell aggregation were diverse between cell lines; however, macrophage aggregation was not associated with levels of TNFα production. 4) Following prolonged culture of THP-1 with HNSCC, THP-1 lost the ability to produce TNFα in response to LPS stimulation.
Conclusions: HNSCC produce soluble and membrane bound proteins that induce TNFα production in macrophages, which convert macrophages into a tolerogenic phenotype. Blocking the tolerogenic pathway could be a novel therapeutic method to limit the progression of oral cancer.