Overexpression of folate binding protein and mesothelin are associated with uterine serous carcinoma

Dainty, Louis A.; Risinger, John I.; Morrison, Carl; Chandramouli, Gadisetti V.R.; Bidus, Michael A.; Zahn, Chris M.; Rose, G. Scott; Fowler, Jeffrey; Berchuck, Andrew; Maxwell, G. Larry

doi:10.1016/j.ygyno.2006.10.063

Cited by 96 publications

(64 citation statements)

References 24 publications

(31 reference statements)

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“…It is commonly expressed in squamous cell carcinomas of different sites such as cervix, lung and head and neck carcinomas as well as endometrial adenocarcinomas. 6,19,20 Mesothelin expression by immunohistochemistry is infrequently present in colorectal, gastric and esophageal cancers. 6 Mesothelin expression is absent in soft tissue sarcomas with the notable exception of biphasic synovial sarcomas.…”

Section: Mesothelin Expression In Other Human Tumorsmentioning

confidence: 99%

Mesothelin targeted cancer immunotherapy

Hassan

2008

European Journal of Cancer

294

258

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Mesothelin is a tumour differentiation antigen that is normally present on the mesothelial cells lining the pleura, peritoneum and pericardium. It is however highly expressed in several human cancers including malignant mesothelioma, pancreatic, ovarian and lung adenocarcinoma. The normal biologic function of mesothelin is unknown but recent studies have shown that it binds to CA-125 and may play a role in the peritoneal spread of ovarian cancer. The limited mesothelin expression in normal tissues and high expression in many cancers makes it an attractive candidate for cancer therapy. Three mesothelin targeted agents are in various stages of clinical evaluation in patients. These include SS1P (CAT-5001) a recombinant immunotoxin targeting mesothelin, MORAb-009 a chimeric anti-mesothelin monoclonal antibody and CRS-207 a live-attenuated Listeria monocytogenes vector encoding human mesothelin. These ongoing clinical trials will help define the utility of mesothelin as a target for cancer therapy.

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Section: Mesothelin Expression In Other Human Tumorsmentioning

confidence: 99%

Mesothelin targeted cancer immunotherapy

Hassan

2008

European Journal of Cancer

294

258

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“…The FR is rarely expressed in normal tissues, 1,2 is highly expressed in breast cancer, endometrial cancer, nonmucinous ovarian adenocarcinoma, lung cancer, kidney cancer, and pancreatic cancer, and is known as a tumor-associated antigen. [3][4][5][6] Folic acid (FA) is a water-soluble B vitamin, and is used in cells to synthesize thymine, which is critical for DNA synthesis, methylation, and repair. Folic acid is small (441 Da), stable over a broad range of temperatures and pH values, inexpensive, and nonimmunogenic.…”

Section: Introductionmentioning

confidence: 99%

Expression of folate receptors in nasopharyngeal and laryngeal carcinoma and folate receptor-mediated endocytosis by molecular targeted nanomedicine

Xie¹,

Zhang²,

Xu³

et al. 2013

IJN

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Abstract:Immunohistochemistry and an immunofluorescence technique was used to detect folate receptor expression in tissue samples and cell lines of head and neck squamous carcinoma, including 20 tissue samples of nasopharyngeal carcinoma, 16 tissue samples of laryngeal carcinoma, and HNE-1, HNE-2, CNE-1, CNE-2, SUNE-1, 5-8F, and Hep-2 cell lines. Iron staining, electron microscopy, and magnetic resonance imaging were used to observe endocytosis of folate-conjugated cisplatin-loaded magnetic nanoparticles (CDDP-FA-ASA-MNP) in cultured cells and transplanted tumors. As shown by immunohistochemistry, 83.3% (30/36) of the head and neck squamous carcinomas expressed the folate receptor versus none in the control group (0/24). Only the HNE-1 and Hep-2 cell lines expressed the folate receptor, and the other five cell lines did not. Endocytosis of CDDP-FA-ASA-MNP was seen in HNE-1 and Hep-2 cells by iron staining and electron microscopy. A similar result was seen in transplanted tumors in nude mice. Magnetic resonance imaging showed low signal intensity of HNE-1 cells and HNE-1 transplanted tumors on T2-weighted images after uptake of CDDP-FA-ASA-MNP, and this was not seen in CNE-2 transplanted tumors. In conclusion, head and neck squamous carcinoma cell strongly expressed the folate receptor, while normal tissue did not. The folate receptor can mediate endocytosis of folate-conjugated anticancer nanomedicines, and lays the foundation for molecular targeted treatment of cancer.

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“…Moreover, mesothelin has been shown to be overexpressed in several cancer types, including mesothelioma, ovarian cancer, and pancreatic cancer (12, 16 -20). Recently, high expressions of mesothelin were detected in lung cancer (21), uterine serous carcinoma (22), and acute myeloid leukemia (23). Little or no expression of mesothelin is seen in other cancer types and normal tissues (12,17,24).…”

Section: Introductionmentioning

confidence: 99%

Mesothelin is a malignant factor and therapeutic vaccine target for pancreatic cancer

Bharadwaj

Zhang

et al. 2008

Molecular Cancer Therapeutics

142

159

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Given the high fatality rate of pancreatic cancer, an effective treatment for this devastating disease is urgently needed. We have shown that mesothelin expression was higher in human pancreatic cancer cells than in human pancreatic duct epithelial cells, and mesothelin mRNA was substantially overexpressed in 18 of 21 (86%) clinical pancreatic adenocarcinoma specimens when compared with the surrounding normal tissues. However, the biological functions of mesothelin in tumor progression are not clearly understood. Here we studied the effects of mesothelin overexpression in pancreatic cancer cell proliferation and migration in vitro and pancreatic cancer progression in vivo. We found that forced expression of mesothelin significantly increased tumor cell proliferation and migration by 90% and 300%, respectively, and increased tumor volume by 4-fold in the nude mice xenograft model when compared with the vector control cell line. Silencing of mesothelin inhibited cell proliferation and migration in pancreatic cancer cells and ablated tumor progression in vivo. Vaccination with chimeric virus-like particles that contain human mesothelin substantially inhibited tumor progression in C57BL/6J mice. The increases in mesothelin-specific antibodies and CTL activity and the decrease in regulatory T cells correlated with reduced tumor progression and prolonged survival. This study revealed novel functions of mesothelin and suggested a new therapeutic vaccine strategy whereby mesothelin is targeted to control pancreatic cancer progression. [Mol Cancer Ther 2008;7(2):286 -96]

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Overexpression of folate binding protein and mesothelin are associated with uterine serous carcinoma

Abstract: Both FOLR1 and MSLN are cell surface targets that are co-expressed at high levels in USC and are appealing targets for biologic therapy.

Cited by 96 publications

References 24 publications

Mesothelin targeted cancer immunotherapy

Mesothelin targeted cancer immunotherapy

Expression of folate receptors in nasopharyngeal and laryngeal carcinoma and folate receptor-mediated endocytosis by molecular targeted nanomedicine

Mesothelin is a malignant factor and therapeutic vaccine target for pancreatic cancer

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