Overexpression of CD147 is associated with poor prognosis, tumor cell migration and ERK signaling pathway activation in hepatocellular carcinoma

Xiao, Wenjing; Zhao, Shufen; Shen, Fangzhen; Liang, Jun; Chen, Jing

doi:10.3892/etm.2017.4818

Cited by 15 publications

(12 citation statements)

References 30 publications

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“…14 The overexpression of CD147 in cancer tissues is correlated with poor prognosis of patients with several types of solid tumors, including esophageal cancer. 15,16 These suggest that the effects of a CD147 targeting agent may result in inhibition of tumor proliferation, invasion, and metastasis.…”

Section: Introductionmentioning

confidence: 99%

Dual effects of an anti-CD147 antibody for Esophageal cancer therapy

Wang

Zhang

Sun³

et al. 2019

Cancer Biology & Therapy

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Background: Esophageal cancer is a highly aggressive neoplasm. Targeted therapy has been proven to be a promising way for cancer therapy. Here, we report a novel anti-CD147 antibody for esophageal cancer therapy, which is a chimeric antibody with modified glycoform in Fc region. Methods: ADCC assay was used to explore the antitumor efficacy of Metuzumab against esophageal cancer in vitro. Wound healing assay and Boyden Chamber invasion assay were performed to explore whether Metuzumab could inhibit migration and invasion of esophageal cancer in vitro. Insulin-like growth factors 1 (IGF-1) and PI3k/Akt was assayed for elaborating antagonistic mechanism of Metuzumab in migration and invasion of esophageal cancer cells. Subcutaneous xenograft nude mouse model was used to investigate the antitumor efficacy of Metuzumab against esophageal cancer in vivo. The esophageal cancer tissue microarrays (TMA) was examined for identification of association of CD147 with lymph node metastasis, and the footpad xenograft nude mouse model was used to explore whether Metuzumab could inhibit lymph node metastasis of esophageal cancer in vivo. Results: The results showed that Metuzumab exhibited higher ADCC compared to the wild type antibody cHAb18. Metuzumab inhibited migration and invasion of esophageal cancer through blockade of CD147 in vitro. The results of Western blot showed Metuzumab might inhibit migration and invasion of esophageal cancer cells through suppressing activation of PI3k/Akt and expression of IGF-1. Experiments in vivo showed that Metuzumab exhibited significant antitumor efficacy and inhibited lymph node metastasis of esophageal cancer in xenograft models. The immunochemical staining of TMA showed CD147 was high-expressed on various kinds of esophageal cancer tissues and associated with the grade of lymph node-metastasis. Conclusions: The in vitro and in vivo study demonstrated dual effects of Metuzumab in effectively mediating ADCC by activating effector cells, and inhibiting metastasis of esophageal cancer through blockade the function of CD147, providing justification for moving Metuzumab forward to clinical development in esophageal cancer.

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Section: Introductionmentioning

confidence: 99%

Dual effects of an anti-CD147 antibody for Esophageal cancer therapy

Wang

Zhang

Sun³

et al. 2019

Cancer Biology & Therapy

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“…Previous studies show that CD147 overexpression may be associated with tumor cell migration and activation of the extracellular-signal-regulated kinase signaling pathway 44 . CD147 has also been proposed as a novel prognostic biomarker for HCC 36 .…”

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confidence: 99%

Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma

et al. 2020

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Chimeric antigen receptor (CAR) therapy is a promising immunotherapeutic strategy for treating multiple refractory blood cancers, but further advances are required for solid tumor CAR therapy. One challenge is identifying a safe and effective tumor antigen. Here, we devise a strategy for targeting hepatocellular carcinoma (HCC, one of the deadliest malignancies). We report that T and NK cells transduced with a CAR that recognizes the surface marker, CD147, also known as Basigin, can effectively kill various malignant HCC cell lines in vitro, and HCC tumors in xenograft and patient-derived xenograft mouse models. To minimize any on-target/off-tumor toxicity, we use logic-gated (log) GPC3–synNotch-inducible CD147-CAR to target HCC. LogCD147-CAR selectively kills dual antigen (GPC3+CD147+), but not single antigen (GPC3-CD147+) positive HCC cells and does not cause severe on-target/off-tumor toxicity in a human CD147 transgenic mouse model. In conclusion, these findings support the therapeutic potential of CD147-CAR-modified immune cells for HCC patients.

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“…Unsurprisingly, differences in protein abundance levels among patient samples were observed. Several of these proteins are associated with roles in cancer migration and invasion, such as CD90 (also known as Thy-1), 36 37 CD147, 38 39 and Homer3. 40 41 Some are associated with growth/tumorigenesis, such as CD98, 42–44 SERCA2, 45 LRBA, 46 and CD166.…”

Section: Discussionmentioning

confidence: 99%

Discovery and validation of surfaceN-glycoproteins in MM cell lines and patient samples uncovers immunotherapy targets

Oldham

Faber

Keppel

et al. 2020

J Immunother Cancer

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BackgroundMultiple myeloma (MM) is characterized by clonal expansion of malignant plasma cells in the bone marrow. While recent advances in treatment for MM have improved patient outcomes, the 5-year survival rate remains ~50%. A better understanding of the MM cell surface proteome could facilitate development of new directed therapies and assist in stratification and monitoring of patient outcomes.MethodsIn this study, we first used a mass spectrometry (MS)-based discovery-driven cell surface capture (CSC) approach to map the cell surface N-glycoproteome of MM cell lines. Next, we developed targeted MS assays, and applied these to cell lines and primary patient samples to refine the list of candidate tumor markers. Candidates of interest detected by MS on MM patient samples were further validated using flow cytometry (FCM).ResultsWe identified 696 MM cell surface N-glycoproteins by CSC, and developed 73 targeted MS detection assays. MS-based validation using primary specimens detected 30 proteins with significantly higher abundance in patient MM cells than controls. Nine of these proteins were identified as potential immunotherapeutic targets, including five that were validated by FCM, confirming their expression on the cell surface of primary MM patient cells.ConclusionsThis MM surface N-glycoproteome will be a valuable resource in the development of biomarkers and therapeutics. Further, we anticipate that our targeted MS assays will have clinical benefit for the diagnosis, stratification, and treatment of MM patients.

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Overexpression of CD147 is associated with poor prognosis, tumor cell migration and ERK signaling pathway activation in hepatocellular carcinoma

Cited by 15 publications

References 30 publications

Dual effects of an anti-CD147 antibody for Esophageal cancer therapy

Dual effects of an anti-CD147 antibody for Esophageal cancer therapy

Efficacy of anti-CD147 chimeric antigen receptors targeting hepatocellular carcinoma

Discovery and validation of surfaceN-glycoproteins in MM cell lines and patient samples uncovers immunotherapy targets

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