Expression and clinical significance of extracellular matrix metalloproteinase inducer, EMMPRIN/CD147, in human osteosarcoma

Lü, Qiang; Lv, Gang; Kim, Andre; Ha, Jong‐Myung; Kim, Suhkman

doi:10.3892/ol.2012.981

Cited by 19 publications

(17 citation statements)

References 40 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Enhanced EMMPRIN expression has been described before in many types of tumor tissues, but was usually not accompanied by detection of EMMPRIN expression on stromal cells (Zhong et al, 2008; Liang et al, 2009; Omi et al, 2012; Pinheiro et al, 2012; Lu et al, 2013), suggesting that stromal cell expression of EMMPRIN in vivo was very low and below the levels of antibody detection. Studies in vitro demonstrated that tumor cells enhance their expression of EMMPRIN when co-cultured with other cell types, such as fibroblasts (Tang et al, 2004; Sato et al, 2009) or endothelial cells (Caudroy et al, 2002; Bougaten et al, 2009), but expression of EMMPRIN in monocytes/macrophages co-cultured with tumor cells was hardly investigated.…”

Section: Discussionmentioning

confidence: 89%

Tumor cell-macrophage interactions increase angiogenesis through secretion of EMMPRIN

Amit-Cohen¹,

Rahat²,

Rahat³

2013

Front. Physiol.

View full text Add to dashboard Cite

Tumor macrophages are generally considered to be alternatively/M2 activated to induce secretion of pro-angiogenic factors such as VEGF and MMPs. EMMPRIN (CD147, basigin) is overexpressed in many tumor types, and has been shown to induce fibroblasts and endothelial cell expression of MMPs and VEGF. We first show that tumor cell interactions with macrophages resulted in increased expression of EMMPRIN and induction of MMP-9 and VEGF. Human A498 renal carcinoma or MCF-7 breast carcinoma cell lines were co-cultured with the U937 monocytic-like cell line in the presence of TNFα (1 ng/ml). Membranal EMMPRIN expression was increased in the co-cultures (by 3–4-folds, p < 0.01), as was the secretion of MMP-9 and VEGF (by 2–5-folds for both MMP-9 and VEGF, p < 0.01), relative to the single cultures with TNFα. Investigating the regulatory mechanisms, we show that EMMPRIN was post-translationally regulated by miR-146a, as no change was observed in the tumoral expression of EMMPRIN mRNA during co-culture, expression of miR-146a was increased and its neutralization by its antagomir inhibited EMMPRIN expression. The secretion of EMMPRIN was also enhanced (by 2–3-folds, p < 0.05, only in the A498 co-culture) via shedding off of the membranal protein by a serine protease that is yet to be identified, as demonstrated by the use of wide range protease inhibitors. Finally, soluble EMMPRIN enhanced monocytic secretion of MMP-9 and VEGF, as inhibition of its expression levels by neutralizing anti-EMMPRIN or siRNA in the tumor cells lead to subsequent decreased induction of these two pro-angiogenic proteins. These results reveal a mechanism whereby tumor cell-macrophage interactions promote angiogenesis via an EMMPRIN-mediated pathway.

show abstract

Section: Discussionmentioning

confidence: 89%

Tumor cell-macrophage interactions increase angiogenesis through secretion of EMMPRIN

Amit-Cohen¹,

Rahat²,

Rahat³

2013

Front. Physiol.

View full text Add to dashboard Cite

show abstract

“…The role of EMMPRIN, also known as CD147, in the process of tumor development, invasion and metastasis is a popular topic in the field of the cellular biology of tumors ( 11 ). The proliferative activity of tumor cells is closely associated with tumor invasion ( 12 ), metastasis ( 13 ) and prognosis ( 14 ).…”

Section: Discussionmentioning

confidence: 99%

Study on extracellular matrix metalloproteinase inducer and human epidermal growth factor receptor-2 protein expression in papillary thyroid carcinoma using a quantum dot-based immunofluorescence technique

Tang

Duanlian

2015

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

The aim of the present study was to investigate the association of extracellular matrix metalloproteinase inducer (EMMPRIN) and human epidermal growth factor receptor (HER)-2 protein expression in papillary thyroid carcinoma with lymph node metastasis (LNM), as well as the correlation between the two types of protein expression. A quantum dot-based immunofluorescence technique was used to detect EMMPRIN and HER-2 protein expression in 75 papillary thyroid carcinoma cases (including 70 cases of papillary thyroid carcinoma tissues and 5 cases of peri-tumor tissues). The positive rate and expression of EMMPRIN and HER-2 were compared and observed. The positive rate of EMMPRIN was 75.71% in papillary thyroid carcinoma tissues and 20.00% in peri-tumor tissues (P<0.05). The positive rate of HER-2 was 45.71% in papillary thyroid carcinoma tissues and 0% in peri-tumor tissues (P>0.05). The expression of EMMPRIN and HER-2 in papillary thyroid carcinoma was significantly associated with LNM (P<0.05). In addition, in the 70 papillary thyroid carcinoma tissues, the expression of EMMPRIN and HER-2 was positively and significantly correlated. In conclusion, this study demonstrates that the co-evolution of EMMPRIN and HER-2 may promote the occurrence and development of papillary thyroid carcinoma and LNM.

show abstract

“…Third, we did not employ any three-dimensional culture systems to examine the effects of microenvironmental factors on spheroidal tumor cell aggregates, which recapitulate in vivo tumor growth more closely; such three-dimensional cellular growth influences cell metabolism and, combined with hypoxia, can increase invasive potential in MG63 cells (41, 42). Finally, as with any in vitro system for the study of malignant tumors, the lack of an extracellular matrix (ECM) precludes the examination of any factors which could contribute further additive effects to tumor cell growth and metastatic potential; in the case of OS, the influences of MMP/TIMP interactions and ECM-associated growth factors on invasive potential have been examined but have not yet been fully elucidated (14, 15, 43–47). However, despite these limitations, this study suggests that tumor microenvironmental factors must be considered in aggregate and that the control of tumor microenvironmental factors, and/or expression of CA IX and VEGF, should be among the important targets for examination in the development of future therapies for malignant tumors.…”

Section: Discussionmentioning

confidence: 99%

Additive Influence of Extracellular pH, Oxygen Tension, and Pressure on Invasiveness and Survival of Human Osteosarcoma Cells

Matsubara¹,

DiResta²,

Kakunaga³

et al. 2013

Front. Oncol.

View full text Add to dashboard Cite

Background/Purpose: The effects of chemical and physical interactions in the microenvironment of solid tumors have not been fully elucidated. We hypothesized that acidosis, hypoxia, and elevated interstitial fluid pressure (eIFP) have additive effects on tumor cell biology and lead to more aggressive behavior during tumor progression. We investigated this phenomenon using three human osteosarcoma (OS) cell lines and a novel in vitro cell culture apparatus.Materials and Methods: U2OS, SaOS, and MG63 cell lines were cultured in media adjusted to various pH levels, oxygen tension (hypoxia 2% O2, normoxia 20% O2), and hydrostatic gage pressure (0 or 50 mmHg). Growth rate, apoptosis, cell cycle parameters, and expression of mRNA for proteins associated with invasiveness and tumor microenvironment (CA IX, VEGF-A, HIF-1A, MMP-9, and TIMP-2) were analyzed. Levels of CA IX, HIF-1α, and MMP-9 were measured using immunofluorescence. The effect of pH on invasiveness was evaluated in a Matrigel chamber assay.Results: Within the acidic–hypoxic–pressurized conditions that simulate the microenvironment at a tumor’s center, invasive genes were upregulated, but the cell cycle was downregulated. The combined influence of acidosis, hypoxia, and IFP promoted invasiveness and angiogenesis to a greater extent than did pH, pO2, or eIFP individually. Significant cell death after brief exposure to acidic conditions occurred in each cell line during acclimation to acidic media, while prolonged exposure to acidic media resulted in reduced cell death. Furthermore, 48-h exposure to acidic conditions promoted tumor invasiveness in the Matrigel assay.Conclusion: Our findings demonstrate that tumor microenvironmental parameters – particularly pH, pO2, and eIFP – additively influence tumor proliferation, invasion, metabolism, and viability to enhance cell survival and must be controlled in OS research.

show abstract

Expression and clinical significance of extracellular matrix metalloproteinase inducer, EMMPRIN/CD147, in human osteosarcoma

Cited by 19 publications

References 40 publications

Tumor cell-macrophage interactions increase angiogenesis through secretion of EMMPRIN

Tumor cell-macrophage interactions increase angiogenesis through secretion of EMMPRIN

Study on extracellular matrix metalloproteinase inducer and human epidermal growth factor receptor-2 protein expression in papillary thyroid carcinoma using a quantum dot-based immunofluorescence technique

Additive Influence of Extracellular pH, Oxygen Tension, and Pressure on Invasiveness and Survival of Human Osteosarcoma Cells

Contact Info

Product

Resources

About