The growth inhibitory effect of human gingiva-derived mesenchymal stromal cells expressing interferon-β on tongue squamous cell carcinoma cells and xenograft model

Abstract

Background Interferon-β (IFN-β) is a cytokine with pleiotropic cellular functions, including antiviral, antiproliferative, and immunomodulatory activities. IFN-β inhibits multiple tumor cell growth in vitro. However, the contradiction between the therapeutic dose of IFN-β and its maximally tolerated dose is still inextricable in vivo. Human gingiva-derived mesenchymal stromal cells (GMSCs) represent promising vehicles for cancer gene therapy. This study evaluated the potential of GMSCs genetically engineered to produce IFN-β as a targeted gene delivery system to treat tongue squamous cell carcinoma (TSCC) in vitro and in vivo. Methods A lentiviral vector encoding IFN-β was constructed and transfected into GMSCs to obtain IFN-β gene-modified GMSCs (GMSCs/IFN-β). Enzyme-linked immunosorbent assay (ELISA) was used to measure the IFN-β concentration in conditioned medium (CM) from GMSCs/IFN-β. The Cell Counting Kit-8 (CCK8), colony formation assay, and flow cytometry were used to detect the effects of GMSCs/IFN-β on TSCC cell line CAL27 cell growth and apoptosis in vitro. TSCC xenograft model was developed by subcutaneous injection of CAL27 cells into BALB/c nude mouse, and the role of intravenously injected GMSCs/IFN-β in engrafting in TSCC and controlling tumor progression was measured in vivo. Results GMSCs/IFN-β expressed a high level of IFN-β. Both CCK8 and colony forming assay showed that GMSCs/IFN-β significantly inhibited the proliferation of CAL27 cells compared with the GMSCs, GMSCs/vector, or DMEM group. Flow cytometry analysis demonstrated that the CAL27 cell apoptosis rate was higher in the GMSCs/IFN-β group than in the other three groups. The in vivo experiment revealed that GMSCs/IFN-β engrafted selectively in TSCC xenograft and expressed a high level of IFN-β. There were smaller tumor volume and lower number of Ki67-positive cells in the GMSCs/IFN-β group than in the GMSCs, GMSCs/vector, or phosphate-buffered saline (PBS) group. Interestingly, GMSCs and GMSCs/vector also presented the potential of CAL27 cell growth inhibition in vitro and in vivo, although such an effect was weaker than GMSCs/IFN-β. Conclusions GMSCs/IFN-β inhibits the proliferation of TSCC cells in vitro and in vivo. These results provide evidence that delivery of IFN-β by GMSCs may be a promising approach to develop an effective treatment option for TSCC therapy.

Nomogram Based on Systemic Immune-Inflammation Index to Predict Survival of Tongue Cancer Patients Who Underwent Cervical Dissection

“…Oral cancer is one of the most common malignant tumors in the head and neck region, and incidence rates are rising around the world (1,2). Tongue squamous cell carcinoma (TSCC) is one of the most aggressive tumors of oral cancers, characterized by high incidence of cervical lymph node metastasis (3). Currently, surgery remains the main treatment choice for localized TSCC, but the prognosis of patients remains unsatisfactory; in some studies, ∼40-60% patients suffer from local recurrence or lymph node metastasis within 5 years, even after curative treatment (4).…”

Stemness Potency of Human Gingival Cells—Application in Anticancer Therapies and Clinical Trials

“…Du et al [68] decided to undertake the same approach and transfected GMSCs with IFNβ. The authors observed that such modified GMSCs significantly inhibited TSCC cells proliferation in vitro and led to their apoptosis.…”

“…The authors observed that such modified GMSCs significantly inhibited TSCC cells proliferation in vitro and led to their apoptosis. After an intravenous injection into the mouse TSCC model, the transfected GMSCs selectively engrafted in TSCC xenograft, which resulted in smaller tumor volume, due to inhibition of tumor cell proliferation, and lower number of Ki-67-positive cells, which is highly expressed in various tumor tissues and used as a marker of tumor cell proliferation [68]. Coccè et al [69] in vitro studies also revealed that GMSCs were able to uptake and release antineoplastic drugs, such as paclitaxel, doxorubicin, and gemcitabine, remaining less sensitive for their antiproliferative activity than cancer cells.…”

“…The authors observed that such modified GMSCs significantly inhibited TSCC cells proliferation in vitro and led to their apoptosis. After an intravenous injection into the mouse TSCC model, the transfected GMSCs selectively engrafted in TSCC xenograft, which resulted in smaller tumor volume, due to inhibition of tumor cell proliferation, and lower number of Ki-67-positive cells, which is highly expressed in various tumor tissues and used as a marker of tumor cell proliferation [ 68 ].…”

Biological roles of Yin Yang 2: Its implications in physiological and pathological events

“…Recent studies demonstrated that IFN‐ β has tumour‐suppressive functions in several types of carcinomas, including triple‐negative breast cancer (TNBC), human colorectal carcinoma and oral squamous cell carcinoma, by activating cytotoxic T lymphocyte in the tumour microenvironment 80‐83 . Activated cytotoxic T lymphocyte will then up‐regulate the host cancer immunosurveillance activity and suppress tumour development 77,84,85 . These facts point to the possibility of YY2 involvement in activating immunosurveillance and performing its tumour‐suppressive effect by maintaining the level of IFN‐ β .…”