Abstract
Simple SummaryBased on its invasiveness, oral squamous cell carcinoma (OSCC) shows two different subtypes: less-invasive verrucous squamous carcinoma (VSCC) or highly invasive squamous cell carcinoma (SCC). The stromal component influences OSCC progression and invasion. On the other hand, bone marrow-derived cells (BMDCs) are recruited into tumors and involved in tumor development. We hypothesized that stromal factors might also affect the relation of BMDCs and tumor invasion. We established the OSCC models transplanted with stromal cells from VSCC and SCC, and we compared the potential stromal factors of VSCC and SCC for the involvement of BMDCs in tumor invasion. Our study showed that stromal factors IL6 and IL1B might promote the contribution of MMP-2 positive BMDCs to OSCC invasion.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.
Highlights
Head and neck cancer is the sixth most common cancer globally
Oral squamous cell carcinoma (OSCC) patientderived stromal cell xenografts (PDSXs) by co-transplanting the stromal cells isolated from patients with different OSCC subtypes: SCC and verrucous OSCC (VSCC) with OSCC cell line (HSC-2) to the Bone marrow transplantation (BMT) nude mice, and we evaluated the infiltration of bone marrow-derived cells (BMDCs) and the expression of
Stroma Architecture Is Different between VSCC- and SCC-patient-derived stroma xenografts (PDSXs) Models
Summary
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]. 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. Technological innovations have helped in the surgical treatment of advanced-stage OSCC and enhanced the efficacy of chemotherapy [4]. The prognosis of OSCC differs according to the subtype. OSCC shows two macroscopic subtypes with the difference in clinical invasion pattern: the endophytic type and the exophytic type [5,6]. The endophytic type is the conventional OSCC (SCC)
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