CD147 silencing via RNA interference reduces tumor cell invasion, metastasis and increases chemosensitivity in pancreatic cancer cells
Central Laboratory, Nanjing First Hospital, Nanjing Medical University, Nanjing, Jiangsu 210006, PR China. Oncology Reports
(Impact Factor: 2.3).
03/2012; 27(6):2003-9. DOI: 10.3892/or.2012.1729
CD147, which belongs to the immunoglobulin superfamily, is a multifunctional glycoprotein that has been shown to increase tumor invasion, metastasis and multidrug resistance. To define the role of CD147 in invasion and metastasis more precisely, we utilized gene silencing to inhibit the expression of CD147 in pancreatic cancer cells. We observed that CD147 expression was significantly impeded at both the mRNA and protein levels and resulted in a decrease of MMP-2 and MMP-9 activities. There was also a decrease of MCT1 expression in the invasion and metastasis potential of pancreatic cancer cells, as well as increased chemosensitivity to gemcitabine in Panc-1 cells. Overall, these results suggest that CD147 plays an important role in the invasion, metastasis and chemosensitivity of the human pancreatic cancer cell line Panc-1, indicating that CD147 may be a promising therapeutic target for pancreatic cancer.
Available from: Danilo Marimpietri
- "Interestingly, Basigin has been identified as a marker of invasion and/or poor prognosis in numerous solid tumors, such as melanoma, prostate, breast, head and neck squamous cell carcinoma, and ovarian cancer –. Inhibition of Basigin expression in both pancreatic cancer cells and a glioblastoma cell line reduced tumor cell invasion, angiogenesis, metastasis and increased chemosensitivity , . Thus, our findings prompt additional studies to investigate the role of basigin in NB growth and invasiveness, as well as the potential relevance of CD147 as a new biomarker in NB patients. "
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ABSTRACT: Neuroblastoma (NB) is the most common extracranial solid tumor in childhood, with grim prognosis in a half of patients. Exosomes are nanometer-sized membrane vesicles derived from the multivesicular bodies (MVBs) of the endocytic pathway and released by normal and neoplastic cells. Tumor-derived exosomes have been shown in different model systems to carry molecules that promote cancer growth and dissemination. In this respect, we have here performed the first characterization and proteomic analysis of exosomes isolated from human NB cell lines by filtration and ultracentrifugation. Electron microscopy demonstrated that NB-derived exosomes exhibited the characteristic cup-shaped morphology. Dynamic light scattering studies showed a bell-shaped curve and a polydispersity factor consistent with those of exosomes. Zeta potential values suggested a good nanoparticle stability. We performed proteomic analysis of NB-derived exosomes by two dimension liquid chromatography separation and mass spectrometry analyses using the multidimensional protein identification technology strategy. We found that the large majority of the proteins identified in NB derived exosomes are present in Exocarta database including tetraspanins, fibronectin, heat shock proteins, MVB proteins, cytoskeleton-related proteins, prominin-1 (CD133), basigin (CD147) and B7-H3 (CD276). Expression of the CD9, CD63 and CD81 tetraspanins, fibronectin, CD133, CD147 and CD276 was validated by flow cytometry. Noteworthy, flow cytometric analysis showed that NB-derived exosomes expressed the GD2 disialoganglioside, the most specific marker of NB. In conclusion, this study shows that NB-derived exosomes express a discrete set of molecules involved in defense response, cell differentiation, cell proliferation and regulation of other important biological process. Thus, NB-derived exosomes may play an important role in the modulation of tumor microenvironment and represent potential tumor biomarkers.
PLoS ONE 09/2013; 8(9):e75054. DOI:10.1371/journal.pone.0075054 · 3.23 Impact Factor
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ABSTRACT: EMMPRIN/CD147 has been proved to be associated with tumor invasion and metastasis in various human malignancies. In the present study, we investigated the expression of CD147 and its association with disease-free survival of colorectal cancer patients. CD147 expression was investigated in 328 cases of colorectal cancer by immunohistochemistry assay. Statistical analysis was utilized to evaluate the association of CD147 expression with disease-free survival of colorectal cancer patients. CD147 expression was proved to be increased in colorectal cancer (P < 0.001) and related to tumor invasion (P < 0.001), metastasis (P < 0.001), and TNM stage (P < 0.001). Kaplan-Meier showed CD147 was associated with disease-free survival of patients with colorectal cancer for patients with higher CD147 expression tend to have shorter disease-free survival (P < 0.001). Multivariate analysis also proved CD147 to be an independent prognostic factor for disease-free survival of colorectal cancer patients (P < 0.05). These results suggested the potential role of CD147 in relapse of human colorectal cancer. It might be a novel molecular marker to predict relapse of patients with colorectal cancer.
Medical Oncology 03/2013; 30(1):369. DOI:10.1007/s12032-012-0369-7 · 2.63 Impact Factor
Available from: Min Cai
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ABSTRACT: Extracellular matrix metalloproteinase inducer (EMMPRIN), also known as CD147, is a member of the immunoglobulin superfamily that is present on the surface of tumor cells and stimulates adjacent fibroblasts to produce matrix metalloproteinases (MMPs). It has been proved to be associated with tumor invasion and metastasis in various human malignancies. In our study, the protein expression level of EMMPRIN in 306 cases of astrocytic glioma is investigated by immunohistochemistry assay. Statistical analysis was utilized to evaluate the association of EMMPRIN with clinicopathological characteristics and prognosis of patients. It was proved that EMMPRIN protein expression was increased in glioma compared with that in normal brain tissue. Moreover, EMMPRIN immunohistochemical staining was correlated with WHO grade and Karnofsky performance score for strong positive EMMPRIN staining is more frequently detected in glioma of advanced grade or low KPS score. It is also demonstrated that EMMPRIN could be an independent negative prognostic factor in glioma for patients with glioma of strong EMMPRIN staining tend to have high risk of death. These results proved that EMMPRIN is associated with prognosis of glioma, which may also suggest the potential role of EMMPRIN in glioma management.
PLoS ONE 03/2013; 8(3):e58069. DOI:10.1371/journal.pone.0058069 · 3.23 Impact Factor
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