Establishment and Characterization of the Human Tongue Squamous Cell Carcinoma Cell Line NOKT-1

Sakuma, Kei; Takahashi, Haruka; Kii, Tomoyuki; Watanabe, Miho; Tanaka, Akira

doi:10.2485/jhtb.30.97

Cited by 2 publications

(2 citation statements)

References 27 publications

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“…Oral squamous cell carcinoma (OSCC) is one of the most common solid tumors of the head and neck ( 1 , 2 ). OSCC consists of 2 major components — malignant epithelium and stroma — which make up the tumor microenvironment (TME) ( 3 – 5 ).…”

Section: Introductionmentioning

confidence: 99%

Resident stroma-secreted chemokine CCL2 governs myeloid-derived suppressor cells in the tumor microenvironment

Oo¹,

Kawai²,

Takabatake³

et al. 2022

JCI Insight

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Accumulating evidence has shown that cancer stroma and bone marrow-derived cells (BMDCs) in the tumor microenvironment (TME) play vital roles in tumor progression. However, the mechanism by which oral cancer stroma recruits any particular subset of BMDCs remains largely unknown. Here we sought to identify the subset of BMDCs that is recruited by cancer stroma. We established a sequential transplantation model in BALB/c nude mice, including (i) bone marrow transplantation of GFP-expressing cells and (ii) co-xenografting of patient-derived stroma (two cases, designated PDS1 and PDS2) with oral cancer cells (HSC-2). As controls, xenografting was performed with HSC-2 alone or in combination with normal human dermal fibroblasts (HDF). PDS1, PDS2, and HDF all promoted BMDCs migration in vitro and recruitment in vivo. Multicolor immunofluorescence revealed that the PDS co-xenografts recruited Arginase-1/CD11b/GR1/GFP quadruple-positive cells, which are myeloid-derived suppressor cells (MDSCs), to the TME, whereas the HDF co-xenograft did not.Screening using microarrays revealed that PDS1 and PDS2 expressed CCL2 mRNA (encoding C-C motif chemokine ligand 2) at higher levels than did HDF. Indeed, PDS xenografts contained significantly higher proportions of CCL2-positive stromal cells and CCR2/Arginase-1/CD11b/GR1 quadruple-positive MDSCs (as receiver cells) than the HDF co-xenograft. Consistently, a CCL2 synthesis inhibitor and a CCR2 antagonist significantly inhibited the PDS-driven migration of BM cells in vitro. Furthermore, intraperitoneal injection of the CCR2 antagonist to the PDS xenograft models significantly reduced the CCR2/Arginase-1/CD11b/GR1 quadruple-positive MDSCs infiltration to the TME. In conclusion, oral cancer stroma-secreted CCL2 is a key signal for recruiting CCR2-positive MDSCs from bone marrow to the TME.

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Section: Introductionmentioning

confidence: 99%

Resident stroma-secreted chemokine CCL2 governs myeloid-derived suppressor cells in the tumor microenvironment

Oo¹,

Kawai²,

Takabatake³

et al. 2022

JCI Insight

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“…Head and neck cancer is the sixth most common cancer globally. Oral squamous cell carcinoma (OSCC) is a common malignant neoplasm of the head and neck region [ 1 , 2 ] which is caused by smoking, snuff, betel quid chewing, alcohol consumption, and viral infection [ 3 ]. The treatment for OSCC is mainly based on the extent of the cancer and includes surgery, chemotherapy, and radiotherapy.…”

Section: Introductionmentioning

confidence: 99%

Cancer-Associated Stromal Cells Promote the Contribution of MMP2-Positive Bone Marrow-Derived Cells to Oral Squamous Cell Carcinoma Invasion

Kawai

Takabatake

et al. 2021

Cancers

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Tumor stromal components contribute to tumor development and invasion. However, the role of stromal cells in the contribution of bone marrow-derived cells (BMDCs) in oral squamous cell carcinoma (OSCC) invasion is unclear. In the present study, we created two different invasive OSCC patient-derived stroma xenografts (PDSXs) and analyzed and compared the effects of stromal cells on the relation of BMDCs and tumor invasion. We isolated stromal cells from two OSCC patients: less invasive verrucous OSCC (VSCC) and highly invasive conventional OSCC (SCC) and co-xenografted with the OSCC cell line (HSC-2) on green fluorescent protein (GFP)-positive bone marrow (BM) cells transplanted mice. We traced the GFP-positive BM cells by immunohistochemistry (IHC) and detected matrix metalloproteinase 2 (MMP2) expression on BM cells by double fluorescent IHC. The results indicated that the SCC-PDSX promotes MMP2-positive BMDCs recruitment to the invasive front line of the tumor. Furthermore, microarray analysis revealed that the expressions of interleukin 6; IL-6 mRNA and interleukin 1 beta; IL1B mRNA were higher in SCC stromal cells than in VSCC stromal cells. Thus, our study first reports that IL-6 and IL1B might be the potential stromal factors promoting the contribution of MMP2-positive BMDCs to OSCC invasion.

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Establishment and Characterization of the Human Tongue Squamous Cell Carcinoma Cell Line NOKT-1

Cited by 2 publications

References 27 publications

Resident stroma-secreted chemokine CCL2 governs myeloid-derived suppressor cells in the tumor microenvironment

Resident stroma-secreted chemokine CCL2 governs myeloid-derived suppressor cells in the tumor microenvironment

Cancer-Associated Stromal Cells Promote the Contribution of MMP2-Positive Bone Marrow-Derived Cells to Oral Squamous Cell Carcinoma Invasion

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