Co-expression of CD147 (EMMPRIN), CD44v3-10, MDR1 and monocarboxylate transporters is associated with prostate cancer drug resistance and progression

Hao, Jingli; Chen, H.; Madigan, Michele C.; Cozzi, Paul; Beretov, Julia; Xiao, Weiwei; Delprado, Warick; Russell, Pamela J.; Li, Yong

doi:10.1038/sj.bjc.6605839

Cited by 103 publications

(96 citation statements)

References 49 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Our flow cytometry results showed much higher expression level of CD147 in CSC-like cells than in NCSCs. Hao et al and Slomiany et al studied CD147 and CD44 expression levels in breast CSCs and found both CD147 and CD44 enriched in CSCs (37)(38)(39). Similar results were observed in our studies.…”

Section: Discussionsupporting

confidence: 82%

Inhibition of CD147 expression by RNA interference reduces proliferation, invasion and increases chemosensitivity in cancer stem cell-like HT-29 cells

Chen

Pan

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

Abstract.The association between CD147 and cancer stem cells (CSCs) provides a new angle for cancer treatments. The aim of this study was to investigate the biological roles of CD147 in colorectal CSCs. The Oct4-green fluorescent protein (GFP) vector was used to isolate CSCs and pYr-mir30-shRNA was used to generate short hairpin RNA (shRNA) specifically for CD147. After RNA interference (RNAi), CD147 was evaluated by reverse transcription-quantitative PCR and western blot analysis, and its biological functions were assessed by MTT and invasion assays. The results showed that the differentiation of isolated CSC-like HT-29 cells was blocked and these cells were highly positive for CD44 and CD147. RNAi-mediated CD147 silencing reduced the expression of CD147 at both mRNA and protein levels. Moreover, the activities of proliferation and invasion were decreased obviously in CSCs. Knockdown of CD147 increased the chemosensitivity of CSC-like cells to gemcitabine, cisplatin, docetaxel at 0.1, 1 and 10 µM respectively, however, there was no significant difference among the three groups to paclitaxel at 10 µM. In conclusion, these results suggest that CD147 plays an important role in colorectal CSCs and might be regarded as a novel CSC-specific targeted strategy against colorectal cancer. IntroductionColorectal cancer, one of the three most common malignancies in the world, remains a major public health problem (1). In 2014, an estimated 71,830 men and 65,000 women were diagnosed with colorectal cancer and 26,270 men and 24,040 women will die of the disease (2). In recent years, remarkable advances have been made in colorectal cancer therapeutic approaches by using chemotherapy, radiotherapy, monoclonal antibodies and small-molecule inhibitors. However, the clinical outcome was far from expected as the effects of these improvements never continued for a long duration (3,4). Therefore, new and better therapies will be the key to reducing the incidence of colorectal cancer.A new emerging concept implicates that treatment failure occurs due to the existence of cancer stem cells (CSCs) that evade the treatment regimen (5,6). These cells had been characterized by pluripotency, self-renewal as well as tumorigenicity (7-9). CSCs were resistant to traditional therapies, leading to tumor recurrence and unpleasant prognosis for cancer patients (10,11). Conventional treatments mainly targeted the tumor cells, but not the CSCs. Thus, therapeutic strategies specifically targeting CSCs could eradicate colorectal cancer more effectively.CSCs were firstly identified in hematopoietic tumors by using cell surface and intracellular molecules (12). Also other types of tumors have been examined for CSCs (13-16). Many studies had chosen specific cell surface markers such as CD19, CD20, CD24, CD44 and CD133 to characterize the subpopulation of CSCs. Transcription factor Oct4 was also typically an intracellular marker (7,(17)(18)(19). Oct4 (also known as OCT3, OCT3/4) belongs to the POU (Pit-Oct-Unc) family of transcription factors. It can form...

show abstract

Section: Discussionsupporting

confidence: 82%

Inhibition of CD147 expression by RNA interference reduces proliferation, invasion and increases chemosensitivity in cancer stem cell-like HT-29 cells

Chen

Pan

et al. 2015

International Journal of Oncology

View full text Add to dashboard Cite

show abstract

“…Overexpression of CD44v3-10, MDR1 and MCT4 was found in most primary prostate cancer tissues, and was significantly associated with prostate cancer progression (29). Another study indicated that the overexpression of CD147, MCT1 and MCT4 is correlated with the progression of epithelial ovarian cancer (EOC) (30).…”

Section: Discussionmentioning

confidence: 95%

Prognostic significance of monocarboxylate transporter 4 expression in patients with colorectal cancer

Nakayama

Torigoe

Inoue

et al. 2011

Experimental and Therapeutic Medicine

View full text Add to dashboard Cite

Abstract. Cancer cells generally have a high rate of glycolysis and produce larger quantities of lactate as compared to the surrounding normal cells. Monocarboxylate transporter 4 (MCT4) is one of the proton pumps exchanging the lactate through the plasma membrane. The prognostic significance of MCT4 expression has not been evaluated in patients with colorectal cancer (CRC). Surgical specimens from 105 CRC patients were immunohistochemically stained using a polyclonal anti-MCT4 antibody. The relationships among the MCT4 expression, clinicopathological factors and prognosis were evaluated. A total of 53 (50.5%) of the 105 patients with CRC were determined to have tumors positive for MCT4 expression. The expression of MCT4 significantly correlated with the tumor size, depth of invasion, lymph node metastasis, distant metastasis and TNM staging. The survival rate of the patients who were positive for MCT4 expression was significantly lower than that of patients with negative MCT4 expression. Positive MCT4 expression was a significantly poor prognostic factor, as determined by both univariate and multivariate analyses. Therefore, positive MCT4 expression appears to be a useful marker for tumor progression and prognosis in patients with CRC.

show abstract

“…MDR1/P-glycoprotein or ABCB1 is one of the well characterized members of the energy-dependent drug efflux pumps that reduce intracellular accumulation of anticancer drugs, leading to the MDR phenotype [26]. Recent studies have demonstrated the co-localization of CD147 with MDR1, highlighting the possible cooperative roles of these molecules in cancer drug resistance and progression [27,28]. In fact, increased expression of CD147 stimulates hyaluronan production, with MDR being induced in a hyaluronan-dependent manner [29,30].…”

Section: A C C E P T E D Accepted Manuscriptmentioning

confidence: 99%

CD147 overexpression allows an accurate discrimination of bladder cancer patients’ prognosis

Afonso

Longatto‐Filho

Baltazar

et al. 2011

European Journal of Surgical Oncology (EJSO)

View full text Add to dashboard Cite

Background Urothelial bladder carcinoma (UBC) is a chemo-sensitive tumour, but the response to treatment is heterogeneous. CD147 has been associated with chemotherapy resistance. We aimed to define tumours with an aggressive phenotype by the combined analysis of clinicopathological and biological parameters.Methods 77 patients with T1G3 or muscle-invasive UBC treated by radical cystectomy were studied. Immunohistochemistry was performed to detect CD147, heparanase, CD31 (blood vessels identification) and D2-40 (lymphatic vessels identification) expressions. The immunohistochemical reactions were correlated with the clinicopathological and the outcome parameters. 5-year disease free survival (DFS) and overall survival (OS) rates were estimated using the Kaplan-Meier method. Multivariate analysis was performed by Cox proportional hazards analysis. ResultsThe 5-year DFS and OS rates were significantly influenced by the classical clinicopathological parameters, and by the occurrence of lymphovascular invasion.CD147 and heparanase immunoexpression did not affect patients' outcome. However, patients with pT3/pT4 tumours had a median OS time of 14.7 months (95% CI 7.1-22.3, p=0.003), which was reduced to 9.2 months (95% CI 1.5-17.0, p=0.008) if the tumours were CD147 positive. We developed a model of tumour aggressiveness using parameters as stage, grade, lymphovascular invasion and CD147 immunoexpression, which separated a low aggressiveness from a high aggressiveness group, remaining as an independent prognostic factor of DFS (HR 3.746; p=0.019) and OS (HR 3.247; 95% CI 1.015-10.388, p=0.047).Conclusion CD147 overexpression, included in a model of UBC aggressiveness, may help surgeons to identify patients who could benefit from a personalized therapeutic regimen. Additional validation is needed.

show abstract

Co-expression of CD147 (EMMPRIN), CD44v3-10, MDR1 and monocarboxylate transporters is associated with prostate cancer drug resistance and progression

Cited by 103 publications

References 49 publications

Inhibition of CD147 expression by RNA interference reduces proliferation, invasion and increases chemosensitivity in cancer stem cell-like HT-29 cells

Inhibition of CD147 expression by RNA interference reduces proliferation, invasion and increases chemosensitivity in cancer stem cell-like HT-29 cells

Prognostic significance of monocarboxylate transporter 4 expression in patients with colorectal cancer

CD147 overexpression allows an accurate discrimination of bladder cancer patients’ prognosis

Contact Info

Product

Resources

About