sCLU as prognostic biomarker and therapeutic target in osteosarcoma

Ma, Jinfeng; Gao, Weiliang; Gao, Jisheng

doi:10.1080/21655979.2019.1621136

Cited by 18 publications

(17 citation statements)

References 34 publications

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“…This may be due to the following aspects: The increased expression levels of sCLU may directly translate to elevated drug resistance, and sCLU may influence the expression of certain other genes and may be associated with the response to other drugs. For instance, various other studies have reported that sCLU was associated with drug resistance of osteosarcoma cells [11] and prostate cancer cells [40]. Furthermore, the increased resistance to drugs was not entirely due to the elevation of sCLU, and is probably regulated by additional signaling pathways, including the activating AKT/GSK3β/β-catenin axis [41] and Wnt/β-catenin and IGF-I signaling [40].…”

Section: Discussionmentioning

confidence: 98%

“…sCLU is found to be overexpressed in osteosarcoma (OS), and sCLU overexpression is associated with metastasis and chemoresistance. Furthermore, targeting sCLU inhibits metastasis and enhances chemosensitivity in OS cells [11]. Aberrant sCLU expression is involved in a number of molecular pathways related to the mechanisms of chemoresistance.…”

Section: Introductionmentioning

confidence: 99%

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Overexpression of secretory clusterin (sCLU) induces chemotherapy resistance in human gastric cancer cells by targeting miR-195-5p

Yang

Guo

et al. 2020

Bioengineered

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Recent focus has turned to secretory clusterin (sCLU) as a key contributor to chemoresistance of anticancer agents, but the role of sCLU on chemotherapy drug response to gastric cancer cells is not fully understood. Previous research found that sCLU was overexpressed in the induced multidrug-resistant MGC-803/5-FU cell line, suggesting that sCLU upregulation was closely related to chemoresistance to anticancer agents. In the present study, we aimed to clarify the role and mechanisms of sCLU in regulating the chemoresistance of gastric cancer cells. Cell apoptosis and cell viability were evaluated by annexin V/propidium iodide staining and CCK8. Expression of sCLU and miR-195-5P was detected using quantitative RT-PCR assays. The expression of sCLU in gastric cancer tissues was detected by RT-PCR assays. Upregulating or downregulating sCLU or miR-195-5P in gastric cancer cells was used to evaluate the mechanisms of chemoresistance. We found that sCLU was significantly elevated in the MGC-803/5-FU and SGC-7901 cells, and the downregulating sCLU sensitized MGC-803/5-FU and SGC-7901 cells to cisplatin and Docetaxel by upregulation of miR-195-5P. Upregulating sCLU in MGC-803 and HGC-27 cells was resistant to cisplatin and Docetaxel by downregulating miR-195-5p. Targeting miR-195-5P reduced the sensitivity of MGC-803 cells to 5-FU, and miR-195-5P overexpression enhanced the sensitivity of MGC-803/5-FU cells to 5-FU. The overexpression of sCLU in gastric cancer tissues was associated with chemoresistance. Our findings suggest that overexpression of sCLU induced chemoresistance in gastric cancer cells by downregulating miR-195-5p, thus providing a potential target for the development of agents that targeting sCLU for gastric cancer therapy.

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Section: Discussionmentioning

confidence: 98%

Section: Introductionmentioning

confidence: 99%

Overexpression of secretory clusterin (sCLU) induces chemotherapy resistance in human gastric cancer cells by targeting miR-195-5p

Yang

Guo

et al. 2020

Bioengineered

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“…It has been demonstrated to physically bind to the taxane drug paclitaxel in ovarian cancer cells, potentially limiting its activity [42]. Exogenously applied clusterin has also been shown to inhibit taxane-mediated microtubule stabilisation, enhance ERK-mediated survival signalling, and promote mitotic progression by inhibiting Cdc25C kinase to limit the action of mitosis-targeting agents [42][43][44][45]. It is unclear whether extracellular clusterin translocates into cells to achieve these effects.…”

Section: Nonenzymatic Proteinsmentioning

confidence: 99%

Tumour Cell Secretome in Chemoresistance and Tumour Recurrence

et al. 2020

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Chemoresistance is a major factor driving tumour relapse and the high rates of cancer-related deaths. Understanding how cancer cells overcome chemotherapy-induced cell death is critical in promoting patient survival. One emerging mechanism of chemoresistance is the tumour cell secretome (TCS), an array of protumorigenic factors released by tumour cells. Chemotherapy exposure can also alter the composition of the TCS, known as therapy-induced TCS, and can promote tumour relapse and the formation of an immunosuppressive tumour microenvironment (TME). Here, we outline how the TCS can protect cancer cells from chemotherapy-induced cell death. We also highlight recent evidence describing how therapy-induced TCS can impact cancer stem cell (CSC) expansion and tumour-associated immune cells to enable tumour regrowth and antitumour immunity. Mechanisms of Tumour Chemoresistance and Relapse: Emerging Role of the Tumour Cell SecretomeChemotherapy is a common and successful therapeutic strategy for many patients with cancer as a neoadjuvant or adjuvant treatment to surgery. However, a significant number of patients relapse months or years later with a tumour that is resistant to further chemotherapeutic challenge, a feature known as chemoresistance. Many relapsing tumours are also associated with distant metastasis, which is the leading cause of cancer-related deaths [1,2]. Therefore, it is critical to identify the mechanisms of chemoresistance to develop targeted therapies and improve the rate of relapsefree survival. Chemoresistance occurs through two mechanisms: intrinsic and acquired resistance. Intrinsic or inherent resistance arises in tumour cells harbouring mutations in cellular processes that prime the cell for survival during chemotherapy treatment. Cancer cells undergoing chemotherapy can also develop or acquire resistance through additional genetic modification or rewiring of intracellular signalling pathways that are known to be crucial for drug resistance [3]. Several key cellular processes are involved in the development of chemoresistance, including drug activation or inactivation, DNA damage repair, modifications to drug targets, enhanced drug efflux, inactivation of apoptosis machinery, and increased autophagy [3,4].Tumour heterogeneity also contributes to a resistant phenotype due to the presence of genetically diverse clones within a tumour. Each of these populations may respond differently to treatment, resulting in the emergence of drug resistant clones. CSCs are a small subpopulation of cancer cells found within the tumour that are another cellular source of chemoresistance. These cells have similar characteristics to nontransformed stem cells, such as the ability to selfrenew, express the embryonic factors Oct4, Sox2, and Nanog, and are capable of differentiating into committed tumour cells. Due to their inherent quiescent state, CSCs can evade the actions of drugs that target rapidly proliferating cells, and can limit drug toxicity due to increased expression of aldehyde dehydrogenase (ALDH), drug e...

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“…CLU was indicated to be elevated in several tumor types. CLU confers chemoresistance to numerous cancer types, including primary breast cancer ( 37 ), pancreatic cancer ( 38 ), lung cancer ( 39 ), osteosarcoma ( 40 ) and prostate cancer ( 41 ). Accordingly, custirsen, a second-generation antisense oligonucleotide, was designed to inhibit the expression of CLU.…”

Section: Discussionmentioning

confidence: 99%

Proteomic profiling of biomarkers by MALDI‑TOF mass spectrometry for the diagnosis of tracheobronchial stenosis after tracheobronchial tuberculosis

et al. 2020

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Tracheobronchial tuberculosis (TB) leads to airway stenosis, irreversible airway damage and even death. The present study aimed to identify biomarkers for the diagnosis of tracheobronchial stenosis (TBS) secondary to tracheobronchial TB. A cohort was recruited, including patients with TBS after tracheobronchial TB, TBS after tracheal intubation or tracheotomy (TIT) and no stenosis of early-stage lung cancer,. Proteomic profiling was performed to gain insight into the mechanisms of the pathological processes. Differentially expressed proteins in the serum and bronchial alveolar lavage fluid (BALF) from patients were detected by matrix-assisted laser desorption ionization time-of-flight mass spectrometry (MALDI-TOF MS). Subsequently, ELISA was performed to validate the changes of protein levels in an additional cohort. MALDI-TOF MS revealed that 8 peptides in the serum, including myeloid-associated differentiation marker, keratin type I cytoskeletal 18, fibrinogen α-chain, angiotensinogen (AGT), apolipoprotein A-I (APOAI), clusterin and two uncharacterized peptides, and nine peptides in BALF, including argininosuccinate lyase, APOAI, AGT and five uncharacterized peptides, were differentially expressed (molecular-weight range, 1,000-10,000 Da) in the TB group compared with the TIT group. The ELISA results indicated that the changes in the protein levels had a similar trend as those identified by proteomic profiling. In conclusion, the present study identified proteins that may serve as potential biomarkers and provide novel insight into the molecular mechanisms underlying TBS after tracheobronchial TB.

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sCLU as prognostic biomarker and therapeutic target in osteosarcoma

Cited by 18 publications

References 34 publications

Overexpression of secretory clusterin (sCLU) induces chemotherapy resistance in human gastric cancer cells by targeting miR-195-5p

Overexpression of secretory clusterin (sCLU) induces chemotherapy resistance in human gastric cancer cells by targeting miR-195-5p

Tumour Cell Secretome in Chemoresistance and Tumour Recurrence

Proteomic profiling of biomarkers by MALDI‑TOF mass spectrometry for the diagnosis of tracheobronchial stenosis after tracheobronchial tuberculosis

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