The Impact of Mesothelin in the Ovarian Cancer Tumor Microenvironment

Our plain-English summary of The Impact of Mesothelin in the Ovarian Cancer Tumor Microenvironment, by T.S. Hilliard (Cancers, 2018).

The study

• Author: T.S. Hilliard
• Journal: Cancers
• Published: 2018;10(9)
• Type of article: Review
• Cited by: 54 articles, as counted by NIH iCite
• Read it: PubMed · Publisher · Free full text

Abstract

Ovarian cancer is the deadliest gynecological disease among U.S. women. Poor 5-year survival rates (<30%) are due to presentation of most women at diagnosis with advanced stage disease with widely disseminated intraperitoneal metastasis. However, when diagnosed before metastatic propagation the overall 5-year survival rate is >90%. Metastasizing tumor cells grow rapidly and aggressively attach to the mesothelium of all organs within the peritoneal cavity, including the parietal peritoneum and the omentum, producing secondary lesions. In this review, the involvement of mesothelin (MSLN) in the tumor microenvironment is discussed. MSLN, a 40kDa glycoprotein that is overexpressed in many cancers including ovarian and mesotheliomas is suggested to play a role in cell survival, proliferation, tumor progression, and adherence. However, the biological function of MSLN is not fully understood as MSLN knockout mice do not present with an abnormal phenotype. Conversely, MSLN has been shown to bind to the ovarian cancer antigen, CA-125, and thought to play a role in the peritoneal diffusion of ovarian tumor cells. Although the cancer-specific expression of MSLN makes it a potential therapeutic target, more studies are needed to validate the role of MSLN in tumor metastasis.

In plain English

This article was a review by a single author of published research on mesothelin, a protein on the cells lining the pleura, pericardium and peritoneum, and its role in how ovarian cancer spreads inside the abdomen. It reported no new experiments or patient data and did not discuss asbestos. The review described earlier studies reporting that mesothelin is normally present in trace amounts but is highly expressed in cancers including 70% of ovarian cancers, mesotheliomas and pancreatic adenocarcinoma. It also noted that mice lacking mesothelin showed no abnormal features. It summarized work showing that mesothelin binds the ovarian cancer marker CA125 with an apparent dissociation constant of 5 nM, which may help tumor cells attach to the abdominal lining. It outlined early clinical trials of mesothelin-targeting treatments; for the immunotoxin SS1P, continuous infusion was well tolerated and showed modest clinical activity. The author concluded that mesothelin is a promising candidate for targeted therapy, but that its role is still poorly understood and further studies are needed to validate its role in tumor metastasis.

We wrote this plain-English summary from the full article with the help of AI, and a second AI model checked each sentence against the article. It is not the authors' wording; the abstract and the article are their own account.

What the study did and found

• Design: Narrative review of published research (no original data)
• Who was studied: No study population; the review covered published laboratory, animal and clinical research on mesothelin, mainly in ovarian cancer, with some mention of mesothelioma and pancreatic cancer
• Exposure: No exposure was studied; the review does not mention asbestos or any fiber type
• Main results:
  • Studies cited in the review reported that mesothelin is normally expressed in trace amounts in mesothelial cells but is highly expressed in cancers including 70% of ovarian cancers, mesotheliomas and pancreatic adenocarcinoma
  • A cited study found that mice lacking mesothelin (knockout mice) had no abnormal phenotype, suggesting mesothelin is not essential
  • Cited studies reported that mesothelin binds CA125 with strong affinity, with an apparent dissociation constant of 5 nM
  • Cited blood-test studies reported that serum mesothelin levels fell after surgical therapy
  • In Phase I trials of the immunotoxin SS1P in mesotheliomas, ovarian and pancreatic cancers, continuous infusion was well tolerated and showed modest clinical activity
  • Patients treated with the anti-mesothelin antibody amatuximab had a rise in CA125 levels, suggesting the drug interferes with mesothelin binding CA125
• The authors' conclusion: The author concluded that the different levels of mesothelin in normal and cancer tissue make it a promising candidate for targeted therapy, but that its role is still poorly understood and further mechanistic studies are needed to validate its role in tumor metastasis
• Limitations the authors state:
  • The author noted that recent studies suggest ovarian cancer may also spread through the blood, but the review discussed only spread by direct shedding of tumor cells
  • The author stated that the biological function of mesothelin is not fully understood

Topics

Medical terms in this study, explained in our Lexicon: Mesothelin, Ovarian Cancer, Tumor Microenvironment, Metastasis, Mesothelium, Peritoneal Cavity, Peritoneum, Omentum.

Related studies

• The Role of Mesothelin Expression in Serous Ovarian Carcinoma: Impacts on Diagnosis, Prognosis, and Therapeutic Targets — G. Giordano, E. Ferioli, et al. (2022)
• Impact of T Cell Ratios on Survival in Pleural Mesothelioma: Insights from Tumor Microenvironment Analysis — L.V. Klotz, A. Weigert, et al. (2024)
• Mesothelin expression remodeled the immune-matrix tumor microenvironment predicting the risk of death in patients with malignant pleural mesothelioma — A.N. Qualiotto, C.M. Baldavira, et al. (2023)
• Low serum mesothelin in pancreatic cancer patients results from retention of shed mesothelin in the tumor microenvironment — X. Zhang, Y. Yu, et al. (2022)
• The impact of γ-irradiation on the induction of bystander killing by genetically engineered ovarian tumor cells: implications for clinical use — J. Zweiri, S.E. Christmas (2017)
• Synergistic Effect of a Mesothelin-Targeted 227Th Conjugate in Combination with DNA Damage Response Inhibitors in Ovarian Cancer Xenograft Models — K. Wickstroem, U.B. Hagemann, et al. (2019)

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