ADAM17 inhibition enhances platinum efficiency in ovarian cancer

Hedemann, Nina; Rogmans, Christoph; Sebens, Susanne; Wesch, Daniela; Reichert, Manuel; Schmidt-Arras, Dirk; Oberg, Hans‐Heinrich; Pecks, Ulrich; Mackelenbergh, Marion van; Weimer, Jörg; Arnold, Norbert; Maass, Nicolaì; Bauerschlag, Dirk

doi:10.18632/oncotarget.24682

Cited by 21 publications

(24 citation statements)

References 55 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…In ovarian cancer cells, miRNA-34c-5p has been shown to directly 31 Similarly, ADAM17 (a disintegrin and metalloprotease 17) belongs to a kind of metalloprotease that can increase the shedding of AR, leading to ovarian cancer cells resistant to cisplatin treatment. 58 In the present study, we found that AR can promote cell mobility and increase Dox resistance in human chondrosarcoma cells.…”

Section: Discussionsupporting

confidence: 55%

Amphiregulin enhances cell migration and resistance to doxorubicin in chondrosarcoma cells through the MAPK pathway

Chen

Huang

Lee

et al. 2018

Molecular Carcinogenesis

View full text Add to dashboard Cite

Chondrosarcoma is characterized by the ability to produce extracellular matrix of cartilage. Curative surgical resection becomes difficult when high-grade chondrosarcoma metastasizes to other parts of the body. Doxorubicin (Dox) has been widely used clinically to treat many different types of cancers, including chondrosarcomas. However, chondrosarcoma is often resistant to chemotherapy and radiotherapy. New systemic treatment regimens are needed to improve the prognosis. Amphiregulin (AR) has been reported to be involved in cancer metastasis and drug resistance. The aim of the present study was to investigate the role of AR on cell migration and Dox sensitivity. To gain insight into the mechanisms used by AR to mediate its effects, we generated two chondrosarcoma cell lines, migration-prone JJ012 and Dox-resistant SW1353, to analyze the relationship between AR levels and cell functions. AR was highly expressed and secreted in mobile and drug-resistant cells. Next, we used the lentivirus-mediated RNAi system to knock down AR expression and found that AR silencing was significantly attenuated in cell migration and drug resistance. In addition, we used exogenous recombinant AR (r-AR) to confirm cell function and we introduced antibody array analysis to investigate pathways of AR activation. The results showed that AR can promote migratory activity and Dox resistance through activation of the MAPK pathway. Whereas the inhibition of the MAPK pathway has the potential to inhibit chondrosarcoma cell migration, p38 inhibition, and ERK activation may render cells more sensitive to Dox. These findings suggest that combining AR with MAPK blockade may effectively treat chondrosarcoma.

show abstract

Section: Discussionsupporting

confidence: 55%

Amphiregulin enhances cell migration and resistance to doxorubicin in chondrosarcoma cells through the MAPK pathway

Chen

Huang

Lee

et al. 2018

Molecular Carcinogenesis

View full text Add to dashboard Cite

show abstract

“…ADAM17 is highly expressed in ovarian cancer cells. When ADAM17 was inhibited in ovarian cancer cell lines using either anti-ADAM17 antibody D1 or GW280264X, the cancer cells were sensitised to cisplatin-induced apoptosis, therefore significantly reducing cell viability [ 68 ].…”

Section: Adam17 Inhibitorsmentioning

confidence: 99%

Implications of ADAM17 activation for hyperglycaemia, obesity and type 2 diabetes

et al. 2021

View full text Add to dashboard Cite

In this review, we focus specifically on the role that the metalloproteinase, A Disintegrin and Metalloproteinase 17 [ADAM17] plays in the development and progression of the metabolic syndrome. There is a well-recognised link between the ADAM17 substrate tumour necrosis factor α (TNF-α) and obesity, inflammation and diabetes. In addition, knocking out ADAM17 in mice leads to an extremely lean phenotype. Importantly, ADAM17-deficient mice exhibit one of the most pronounced examples of hypermetabolism in rodents to date. It is vital to further understand the mechanistic role that ADAM17 plays in the metabolic syndrome. Such studies will demonstrate that ADAM17 is a valuable therapeutic target to treat obesity and diabetes.

show abstract

“…Along this line, EMT has been suggested to be a prerequisite for muscle invasion/metastasis in bladder cancer [ 33 ], although the role of ADAMs in BCG-refractory bladder cancer has not been addressed in this study. Additionally, ADAM17 was shown to be enhanced by platinum-based chemotherapy and caused EGFR transactivation by stimulating AREG release [ 34 ]. In this context, ADAM17 inhibition sensitized cancer cells to cisplatin-induced apoptosis.…”

Section: Discussionmentioning

confidence: 99%

Expression of ADAM Proteases in Bladder Cancer Patients with BCG Failure: A Pilot Study

Pichler

Lindner

Schäfer

et al. 2021

JCM

View full text Add to dashboard Cite

Although Bacillus Calmette Guérin (BCG) remains a mainstay of adjuvant treatment in high-risk, non-muscle-invasive bladder cancer, BCG failure occurs in up to 40% of patients, with radical cystectomy (RC) as the inevitable therapeutic consequence. Current data suggest that PD-L1 immunosuppressive signaling is responsible for BCG failure, supporting the therapeutic rationale of combining checkpoint inhibitors with BCG. To address the immune cascade in 19 RC specimens obtained after BCG failure, we applied a small immunohistochemical (IHC) panel consisting of selected markers (PD-L1, GATA-3, a disintegrin and metalloproteinase (ADAM) proteases, IL-10/IL-10R). A modified quick score was used for IHC semi-quantification of these markers in tumor cells (TC) and immune cells (IC) within two different regions: muscle-invasive bladder cancer (MIBC) and primary/concurrent carcinoma in situ (CIS). Contrary to expectation, PD-L1 was consistently low, irrespective of tumor region and cell type. Intriguingly, expression of ADAM17, which has been reported to release membrane-bound PD-L1, was high in both tumor regions and cell types. Moreover, expression of GATA3, IL-10, and IL-10R was also increased, indicative of a generally immunosuppressive tumor microenvironment in BCG failure. ADAM10 expression was associated with advanced tumor disease at RC. Our findings raise the possibility that ADAM proteases may cleave PD-L1 from the surface of bladder TC and possibly also from IC. Therefore, IHC assessment of PD-L1 expression seems to be insufficient and should be supplemented by ADAM10/17 in patients with BCG failure.

show abstract

ADAM17 inhibition enhances platinum efficiency in ovarian cancer

Cited by 21 publications

References 55 publications

Amphiregulin enhances cell migration and resistance to doxorubicin in chondrosarcoma cells through the MAPK pathway

Amphiregulin enhances cell migration and resistance to doxorubicin in chondrosarcoma cells through the MAPK pathway

Implications of ADAM17 activation for hyperglycaemia, obesity and type 2 diabetes

Expression of ADAM Proteases in Bladder Cancer Patients with BCG Failure: A Pilot Study

Contact Info

Product

Resources

About