EMMPRIN reduction via scFv-M6-1B9 intrabody affects α3β1-integrin and MCT1 functions and results in suppression of progressive phenotype in the colorectal cancer cell line Caco-2

Sangboonruang, Sirikwan; Thammasit, Patcharin; Intasai, Nutjeera; Kasinrerk, Watchara; Tayapiwatana, Chatchai; Tragoolpua, Khajornsak

doi:10.1038/cgt.2014.24

“…[39][40][41] CFs produce a variety of cytokines, such as IL-6, endothelin-1, and insulin-like growth factor-1, all of which induce hypertrophic response in cardiomyocytes in a paracrine manner. 40,42,43 In this study, we demonstrated that cell surface Bsg is cleaved and secreted from CFs in response to stimulus by mechanical stretch and Ang II. Moreover, treatment with hrBsg activated mitogen-activated protein kinase in CFs and promoted cell proliferation.…”

Section: Inflammatory Response Of Cfs To Pressure Overloadmentioning

confidence: 59%

Basigin Promotes Cardiac Fibrosis and Failure in Response to Chronic Pressure Overload in Mice

Suzuki

¹

,

Satoh

²

,

Ikeda

³

et al. 2016

ATVB

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Objective— Basigin (Bsg) is a transmembrane glycoprotein that activates matrix metalloproteinases and promotes inflammation. However, the role of Bsg in the pathogenesis of cardiac hypertrophy and failure remains to be elucidated. We examined the role of Bsg in cardiac hypertrophy and failure in mice and humans. Approach and Results— We performed transverse aortic constriction in Bsg +/– and in wild-type mice. Bsg +/– mice showed significantly less heart and lung weight and cardiac interstitial fibrosis compared with littermate controls after transverse aortic constriction. Both matrix metalloproteinase activities and oxidative stress in loaded left ventricle were significantly less in Bsg +/– mice compared with controls. Echocardiography showed that Bsg +/– mice showed less hypertrophy, less left ventricular dilatation, and preserved left ventricular fractional shortening compared with littermate controls after transverse aortic constriction. Consistently, Bsg +/– mice showed a significantly improved long-term survival after transverse aortic constriction compared with Bsg +/+ mice, regardless of the source of bone marrow ( Bsg +/+ or Bsg +/– ). Conversely, cardiac-specific Bsg-overexpressing mice showed significantly poor survival compared with littermate controls. Next, we isolated cardiac fibroblasts and examined their responses to angiotensin II or mechanical stretch. Both stimuli significantly increased Bsg expression, cytokines/chemokines secretion, and extracellular signal–regulated kinase/Akt/JNK activities in Bsg +/+ cardiac fibroblasts, all of which were significantly less in Bsg +/– cardiac fibroblasts. Consistently, extracellular and intracellular Bsg significantly promoted cardiac fibroblast proliferation. Finally, serum levels of Bsg were significantly elevated in patients with heart failure and predicted poor prognosis. Conclusions— These results indicate the crucial roles of intracellular and extracellular Bsg in the pathogenesis of cardiac hypertrophy, fibrosis, and failure in mice and humans.

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“…In our study, we demonstrated earlier that chimeric adenovirus 5/F35 carrying gene encoding scFv against EMMPRIN (Ad5/F35- scFv-M6-1B9 ) is effective in diminishing EMMPRIN cell surface expression and subsequently decreasing cancer cell proliferation, invasion, and metastasis in the colorectal cancer cell line, Caco-2 31 . However, the apoptotic effect of reducing EMMPRIN cell surface levels using intrabody technique in established colorectal cancer cells has hitherto been unclear.…”

Section: Introductionmentioning

confidence: 64%

“…Our previous study revealed for the first time that scFv-M6-1B9 intrabody has the ability to down-regulate EMMPRIN cell surface expression on colorectal cancer cell, Caco-2, via flow cytometry 31 . To confirm the reduction of the EMMPRIN cell surface expression due to its accumulation inside the cells, immunoblotting was performed.…”

Section: Resultsmentioning

confidence: 97%

See 1 more Smart Citation

Intracellular Acidosis Promotes Mitochondrial Apoptosis Pathway: Role of EMMPRIN Down-regulation via Specific Single-chain Fv Intrabody

Thammasit¹,

Sangboonruang²,

Suwanpairoj³

et al. 2015

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Extracellular matrix metalloproteinase inducer (EMMPRIN) is a human leukocyte surface molecule that is enriched on the surface of many cancer cells, and it plays an important role in proliferation and metastasis. In this study, we utilized the chimeric adenoviral vector Ad5/F35 carrying gene encoding scFv against EMMPRIN (scFv-M6-1B9) to down-regulate EMMPRIN cell surface expression and investigated programmed cell death response in colorectal cancer (CRC) cell, Caco-2. The scFv-M6-1B9 intrabody exhibits robust activity in reducing EMMPRIN cell surface expression. This approach led to the inducing of apoptosis, which was relative to the increasing of apoptotic bodies in sub-G1 peak, phosphatidylserine externalization, as well as TUNEL-positive cells. In addition, real-time RT-PCR and western blotting analysis indicated that apoptosis was enhanced through the mitochondrial pathway, a marked reduction of Bcl-2, leading to the translocation of cytochrome c and also the dramatic activation of caspase-3. Moreover, carcinoembryonic antigen (CEA), a tumor marker for CRC, was found to have significantly diminished in both secreted protein and mRNA levels. In conclusion, these findings suggest that EMMPRIN down-regulation by scFv-M6-1B9 intrabody has great potential in enhancing the efficacy of apoptosis induction through the mitochondrial pathway and in effecting a decline in the CEA level. Thus, its benefits could be applied to project the future prospects for targeted gene therapy and therapeutic application in monitoring colorectal cancer.

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“…For example, siRNA targeting CD147 inhibits the invasion of human cervical squamous carcinoma cells [103]. The intrabody scFv-M6-1B9 can reduce CD147 cell surface expression in a colorectal cancer cell line (Caco-2), which leads to subsequent suppression of tumor progression, including cell migration, proliferation and invasion [104]. Therefore, agents such as antisense RNAs, intrabody and antibody drugs against CD147 that intervene in CD147 functions may have possible therapeutic effects in the prevention and treatment of glioma progression.…”

Section: Resultsmentioning

confidence: 99%

The roles of CD147 in the progression of gliomas

Fei

¹

,

Li

²

,

Zhou

³

et al. 2015

Expert Review of Anticancer Therapy

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Gliomas are characterized by their invasiveness, angiogenesis, glycolysis and poor prognosis. Determining how to inhibit angiogenesis and glycolysis and induce cell death in gliomas is essential to the development of an effective therapy. CD147, a highly glycosylated transmembrane glycoprotein with two Ig-like extracellular domains that belongs to the immunoglobulin superfamily, plays an important role in the regulation of tumor invasiveness, angiogenesis and glycolysis by inducing the secretion of matrix metalloproteinases and vascular endothelial growth factor and by interacting with monocarboxylate transporters. In this review, we first summarize the roles played by CD147 in gliomas and then propose that CD147 may be a complementary prognostic biomarker and a possible therapeutic target for glioma treatment.

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EMMPRIN reduction via scFv-M6-1B9 intrabody affects α3β1-integrin and MCT1 functions and results in suppression of progressive phenotype in the colorectal cancer cell line Caco-2

Cited by 11 publications

References 58 publications

Basigin Promotes Cardiac Fibrosis and Failure in Response to Chronic Pressure Overload in Mice

Basigin Promotes Cardiac Fibrosis and Failure in Response to Chronic Pressure Overload in Mice

Intracellular Acidosis Promotes Mitochondrial Apoptosis Pathway: Role of EMMPRIN Down-regulation via Specific Single-chain Fv Intrabody

The roles of CD147 in the progression of gliomas

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