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

SIMPLE SUMMARY: Based 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. ABSTRACT: 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.