Hitting the Bull’s-Eye: Mesothelin’s Role as a Biomarker and Therapeutic Target for Malignant Pleural Mesothelioma

Yeo, Dannel; Castelletti, Laura; Zandwijk, Nico van; Rasko, John E.J.

doi:10.3390/cancers13163932

Cited by 18 publications

(19 citation statements)

References 148 publications

(179 reference statements)

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“…MSLN has been widely studied in a variety of tumors ( 40 – 43 ). However, MSLN in ovarian cancer and immune-related bioinformatics research is still rare.…”

Section: Discussionmentioning

confidence: 99%

MSLN Correlates With Immune Infiltration and Chemoresistance as a Prognostic Biomarker in Ovarian Cancer

Tian

Zhang

et al. 2022

Front. Oncol.

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Mesothelin (MSLN) is a glycoprotein with various expression degrees in different tumors including mesothelioma, ovarian cancer, pancreatic cancer, etc. MSLN is considered to play an important role in cell survival, proliferation, and tumor progression. Although the expression of MSLN in tumors makes it a potential therapeutic target, its mechanism of action is still unclear, especially its correlation with immune cells infiltration in the tumor microenvironment has not been investigated. In this study, we detected the overexpression of MSLN in ovarian cancer using database analysis and tissue-array staining. We further evaluated the diagnostic value of MSLN and found it was associated with poor overall survival in ovarian cancer. In addition, the high expression of MSLN was significantly related to the immune-related genes and chemoresistant genes. We confirmed the overexpression of MSLN in the chemoresistant ovarian cancer cell lines. Our research suggests that MSLN participates in a variety of pathways related to the suppression of immune activation and promotion of chemoresistance, leading to a poor prognosis in ovarian cancer.

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“…MSLN has been widely studied in a variety of tumors ( 40 – 43 ). However, MSLN in ovarian cancer and immune-related bioinformatics research is still rare.…”

Section: Discussionmentioning

confidence: 99%

MSLN Correlates With Immune Infiltration and Chemoresistance as a Prognostic Biomarker in Ovarian Cancer

Tian

Zhang

et al. 2022

Front. Oncol.

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“…Antibodies against ECM proteins such as fibulin-3 would have the advantage of excellent accessibility to targets that are outside the tumor cells, as well as the possibility of being delivered locally in the pleural cavity, maximizing intratumoral accumulation. It is worth noting that recombinant antibodies against mesothelin, which has a cleaved soluble isoform that accumulates in the tumor matrix, have already been tested in the clinical setting ( 60 ). Similarly, chimeric antibodies against podoplanin, an ECM-associated protein that is another proposed MPM biomarker, have been validated in clinically-relevant MPM models (e.g., ( 61 )).…”

Section: Discussionmentioning

confidence: 99%

The extracellular matrix protein fibulin-3/EFEMP1 promotes pleural mesothelioma growth by activation of PI3K/Akt signaling

et al. 2022

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Malignant pleural mesothelioma (MPM) is an aggressive tumor with poor prognosis and limited therapeutic options. The extracellular matrix protein fibulin-3/EFEMP1 accumulates in the pleural effusions of MPM patients and has been proposed as a prognostic biomarker of these tumors. However, it is entirely unknown whether fibulin-3 plays a functional role on MPM growth and progression. Here, we demonstrate that fibulin-3 is upregulated in MPM tissue, promotes the malignant behavior of MPM cells, and can be targeted to reduce tumor progression. Overexpression of fibulin-3 increased the viability, clonogenic capacity and invasion of mesothelial cells, whereas fibulin-3 knockdown decreased these phenotypic traits as well as chemoresistance in MPM cells. At the molecular level, fibulin-3 activated PI3K/Akt signaling and increased the expression of a PI3K-dependent gene signature associated with cell adhesion, motility, and invasion. These pro-tumoral effects of fibulin-3 on MPM cells were disrupted by PI3K inhibition as well as by a novel, function-blocking, anti-fibulin-3 chimeric antibody. Anti-fibulin-3 antibody therapy tested in two orthotopic models of MPM inhibited fibulin-3 signaling, resulting in decreased tumor cell proliferation, reduced tumor growth, and extended animal survival. Taken together, these results demonstrate for the first time that fibulin-3 is not only a prognostic factor of MPM but also a relevant molecular target in these tumors. Further development of anti-fibulin-3 approaches are proposed to increase early detection and therapeutic impact against MPM.

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“…However, in MPM, MSLN is known to be associated with epithelial–mesenchymal transition (EMT) and binding to mucin 16 (MUC16/CA125), which is associated with cancer progression and aggressiveness [ 69 , 70 ]. MSLN is highly expressed in tumors, while its expression in normal cells is limited, making it a promising biomarker and therapeutic target [ 71 , 72 ]. NIR-PIT targeting MSLN was effective in a mouse xenograft model [ 73 ].…”

Section: Exploring Other Targets To Detect More Specific and Effectiv...mentioning

confidence: 99%

Near-Infrared Photoimmunotherapy for Thoracic Cancers: A Translational Perspective

et al. 2022

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The conventional treatment of thoracic tumors includes surgery, anticancer drugs, radiation, and cancer immunotherapy. Light therapy for thoracic tumors has long been used as an alternative; conventional light therapy also called photodynamic therapy (PDT) has been used mainly for early-stage lung cancer. Recently, near-infrared photoimmunotherapy (NIR-PIT), which is a completely different concept from conventional PDT, has been developed and approved in Japan for the treatment of recurrent and previously treated head and neck cancer because of its specificity and effectiveness. NIR-PIT can apply to any target by changing to different antigens. In recent years, it has become clear that various specific and promising targets are highly expressed in thoracic tumors. In combination with these various specific targets, NIR-PIT is expected to be an ideal therapeutic approach for thoracic tumors. Additionally, techniques are being developed to further develop NIR-PIT for clinical practice. In this review, NIR-PIT is introduced, and its potential therapeutic applications for thoracic cancers are described.

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Hitting the Bull’s-Eye: Mesothelin’s Role as a Biomarker and Therapeutic Target for Malignant Pleural Mesothelioma

Cited by 18 publications

References 148 publications

MSLN Correlates With Immune Infiltration and Chemoresistance as a Prognostic Biomarker in Ovarian Cancer

MSLN Correlates With Immune Infiltration and Chemoresistance as a Prognostic Biomarker in Ovarian Cancer

The extracellular matrix protein fibulin-3/EFEMP1 promotes pleural mesothelioma growth by activation of PI3K/Akt signaling

Near-Infrared Photoimmunotherapy for Thoracic Cancers: A Translational Perspective

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