Inhibition of CD147 gene expression via RNA interference reduces tumor cell invasion, tumorigenicity and increases chemosensitivity to cisplatin in laryngeal carcinoma Hep2 cells

Abstract

Abstract. CD147, also named extracelluar matrix metalloproteinase inducer (EMMPRIN), is a member of the immunoglobulin family and a glycoprotein enriched on the surface of tumor cells, which promotes invasion, metastasis, growth and survival of malignant cells, and is known to confer resistance to some chemotherapeutic drugs. To determine the possible role of CD147 in the invasive properties of laryngeal carcinoma, we used an RNA interference approach to silence CD147 expression in the Hep2 cell line at high levels of CD147 expression. Our results showed that CD147 expression was significantly impeded at both mRNA and protein levels, which resulted in a decrease of the Hep2 invasion activity in vitro and tumorigenicity in nude mice. The suppression of CD147 expression also sensitized cells to cisplatin. Our current results indicated that CD147 was a laryngeal carcinoma-related gene and CD147 might be a potential target for therapeutic anti-cancer drugs. IntroductionLaryngeal carcinoma is the 11th commonest form of cancer in men worldwide, with 121,000 new cases in 1985 (1). It is one of the most common malignancies in Europe, with about 52,000 new cases per year (2), approximately 9,500-11,000 new cases of laryngeal cancer are estimated to occur yearly in the United States (3,4). It is also very common in the northeast of China in recent years, and has shown increasing tendency (5). Laryngeal carcinoma especially at late-stage is associated with high morbidity and poor long-term survival due to the absence of effective treatment methods. Thus, better understanding of molecular mechanisms underlying proliferation, invasion and survival of laryngeal carcinoma is critical for the development of optimal therapeutic modalities. Recent studies suggest that CD147 is highly expressed in laryngeal carcinomas (6,7). CD147 (also known as EMMPRIN, basigin, M6 and tumor cell derived collagenase stimulatory factor), a highly glycosylated transmembrane protein that belongs to the immunoglobulin superfamily (8), is widely expressed and enriched on the surface of many malignant tumor cells. These cancers include breast cancer, lymphoma, oral squamous cell carcinoma, glioma, melanoma, lung, and bladder and kidney carcinomas (9-11). CD147 plays an important role in tumor formation and invasion/metastasis in both animal models (12) and cancer patients (13).The metastatic potential of cancerous cells is dependent upon their ability to disengage themselves from environmental cues that serve to regulate and constrain them. CD147 is found overexpressed in a number of cancerous specimens, coupled with its ability to induce matrix metalloproteinase (MMPs) expression (14). MMPs are a family of zincdependent endopeptidases which currently consists of more than 25 members. According to sequence homologies and related substrate preferences, MMPs can be divided into 5 subfamilies, collagenases, gelatinases, tromelysins, membrane-type MMPs, and others. MMPs expression allows degradation of the basement membrane that are believed to affect tumo...

EMMPRIN Expression in Oral Squamous Cell Carcinomas: Correlation with Tumor Proliferation and Patient Survival

“…These results are in line with ours, suggesting that EMMPRIN might be relevant for the tumor proliferation and tumor growth of OSCC. Furthermore, knockdown of EMMPRIN in head and neck carcinomas decreased cellular proliferation and tumor growth in vitro and in vivo analyses [28–30]. Mechanisms involved in tumor proliferation via EMMPRIN are poorly understood, but some authors have described the role of this receptor in association with cyclophilin A in the activation of ERK1/2 and p38 pathways [31].…”

The role of EMMPRIN expression in ovarian epithelial carcinomas

“…Membranous EMMPRIN expression, but not the overall EMMPRIN expression, was associated with poor response to cisplatin-based chemotherapies and a poor prognosis in advanced patients with non-small-cell lung carcinoma 48 . Silencing EMMPRIN increased the proliferation-inhibiting effect of cisplatin to lung cancer A549/DDP, 42 laryngeal carcinoma Hep2, 49 and gastric carcinoma SG7901 50 cells. However, we found no difference in EMMPRIN expression between ovarian carcinoma SKOV3 and SKOV3/DDP.…”

SDF‑1/CXCR4 induces cell invasion through CD147 in squamous cell carcinoma of the hypopharynx

“…This was similar to the result of a study that used oral cancer cells ( 16 ). On the other hand, it was reported that CXCR4 was not involved in cell proliferation in HEp-2, an SCC of the larynx cell line ( 43 ). Therefore, these reports indicate that CXCR4 has different effects depending on the sub-location even within the same type of head and neck cancer and that detailed examination is necessary depending on the tumor site.…”