How is cancer related to mpf

To date, no MPF receptor has been identified on megakaryocytes or any other cells. Neither have theories been put forward to explain why a protein normally expressed exclusively by mesothelial cells should have a primary function as a megakaryocyte stimulating factor.

Interestingly, in our experiments, while MPF increased tumor aggressiveness in vivo , forced overexpression of MPF produced no growth advantage in vitro. This suggests that the effect of MPF on tumor aggressiveness is not mediated by a direct action of MPF on the tumor, but perhaps by working indirectly on other cells.

Although it might be tempting to consider that MPF may have an immune effector function, our experiments were conducted in lymphocyte-deficient mice, suggesting that another mechanism is more likely to be responsible.

Identification of the cell type s responsible for mediating this effect of MPF is beyond the scope of the current study.

Although our observations were made using a single cell type, the effect we observed on survival was profound and highly reproducible. Our data suggest that MPF could be an important mediator of tumor aggressiveness in the peritoneal cavity, and that inhibition or sequestration of MPF might be clinically useful in slowing the growth of some cancers that grow in the peritoneal cavity. Studies to test this hypothesis have been initiated.

Conceived and designed the experiments: RH IP. Analyzed the data: RH IP. Browse Subject Areas? Click through the PLOS taxonomy to find articles in your field. Adusumilli, Memorial Sloan-Kettering Cancer Center, United States of America Received: April 24, ; Accepted: July 12, ; Published: August 13, This is an open-access article, free of all copyright, and may be freely reproduced, distributed, transmitted, modified, built upon, or otherwise used by anyone for any lawful purpose.

Introduction The mesothelin MSLN gene encodes a lineage restricted tumor antigen that is expressed in normal mesothelial cells lining the pleura, peritoneum and pericardium. Download: PPT. Figure 1. Statistical Analysis For survival studies, Kaplan-Meier curves were plotted and compared using the log-rank test. Results Previous studies have shown that mMSLN interacts with the ovarian cancer tumor antigen CA and that this interaction may be important in metastatic spread of ovarian cancer through the peritoneal cavity [8] , [16] , [19].

Figure 2. Figure 3. Figure 4. Table 1. Table 2. Colony formation of stably transfected A cells in soft agar. Discussion For our study, we created a mouse model that lacks the Msln gene and is permissive to the growth of human cancer cells. References 1. Clin Cancer Res — View Article Google Scholar 2. View Article Google Scholar 3. Breast Cancer Res Treat — View Article Google Scholar 4. Identification of a new pancreataic cancer marker by serial analysis of gene expression SAGE.

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Scand J Clin Lab Invest , — Download references. The authors wish to thank Jennifer Werkheiser for expert assistance in the preparation of this manuscript. Department of Diagnostics Development, Morphotek, Inc. Frontage Laboratories, Inc. You can also search for this author in PubMed Google Scholar. DJO and ES conceived and designed the experiments. All authors read and approved the final manuscript.

Reprints and Permissions. Serum folate receptor alpha, mesothelin and megakaryocyte potentiating factor in ovarian cancer: association to disease stage and grade and comparison to CA and HE4. J Ovarian Res 6, 29 Download citation.

Received : 27 February Accepted : 09 April Published : 17 April Anyone you share the following link with will be able to read this content:. Sorry, a shareable link is not currently available for this article. Provided by the Springer Nature SharedIt content-sharing initiative. Skip to main content. Search all BMC articles Search. Download PDF. Conclusions FRA has significant potential as a biomarker for ovarian cancer, both as a stand-alone marker and in combination with other known markers for EOC.

Background In , it is estimated that 22, women will be diagnosed with ovarian cancer and 15, will die of the disease SEER fact sheet. Materials and methods Patient samples and controls Samples were obtained from various commercial vendors with Institutional Review Board approvals and patient consent and were collected between and Table 1 Characteristics of patients and controls Full size table. Figure 1. Full size image. Figure 2.

Table 2 Biomarker serum levels with clinicopathological findings in ovarian cancer patients Full size table. Because the tumor is difficult to diagnose and the initial symptoms can be insidious, the disease is often diagnosed at an advanced stage, and this delay is associated with a median survival of about 12 months 5 , Moreover, MM, in general, is poorly responsive to current therapies, but this is especially true in advanced stages of the disease.

Monotherapy and combination therapy have been widely investigated for the treatment of MM however, all therapeutic strategies failed to significantly benefit patients so far 25 - On the other hand, it has been shown that when patients are diagnosed and treated at an early stage stage I of MM, the overall median survival is significantly improved 29 , Therefore, the relevance of early diagnosis of MM is very high for a better response to therapy.

Monitoring cohorts at high risk of developing MM, because of documented exposure to asbestos or other mineral fibers, or because they carry germline BAP1 mutations, can be a helpful strategy to make MM diagnoses at earlier stages, when the malignancy may be more susceptible to therapy. A biomarker generally refers to a measurable indicator of some biological state or condition, including a pathogenic process. Different novel biomarkers have been utilized in pre-clinical studies and diagnosis to predict, detect and monitor cancers along several last decades.

An ideal biomarker should selectively detect MM patients from other malignancies or asbestos-exposed subjects from non-exposed individuals. The ideal sample types for detecting biomarkers are blood and pleural effusion PE , which can be easily collected. This review focuses on some of the most frequently used and promising biomarkers for early detection and diagnosis of MM. Mesothelin is a kDa precursor protein, which is physiologically cleaved into two mature proteins: the kDa NH2-terminal megakaryocyte potentiating factor MPF , secreted into the blood, and the kDa COOH-terminal glycosylated phosphatidylinositol-linked glycoprotein, which is a plasma membrane-bound protein.

Mesothelin is expressed at low levels in normal mesothelial cells and is undetectable in most normal tissues. On the contrary, mesothelin is overexpressed in several human cancers, including MM 33 , 34 , pancreatic adenocarcinoma 35 , ovarian 36 and lung cancers Furthermore, it has been proposed that serum SMRPs levels may also differentiate MM patients from patients with pleural metastases of different types of carcinomas 39 , 40 , However, serum mesothelin levels are elevated also in patients with renal impairment, and therefore renal function has to be taken into account during the interpretation of this assay A systematic review and meta-analysis of 12 studies in MM patients and 2, control subjects including healthy control and patients with non-MM diseases.

The meta-analysis of Hollevoet et al. These results indicate that, although SMRPs may help to identify MM, the sensitivity of the assay is inadequate, limiting its application in early diagnosis of MM Higher serum MPF levels were detected in MM patients, compared to healthy subjects, individuals with benign asbestos-related diseases, or lung cancer patients 48 , This study enrolled participants, grouped into six cohorts: healthy controls, 46 individuals with benign respiratory disease, 89 healthy asbestos-exposed individuals, patients with benign asbestos-related diseases, 63 lung cancer and 85 MM patients.

The definition of the approaches to account for these covariates requires further validation OPN is a secreted glycoprotein that plays critical roles in several biological processes, such as cell-matrix interaction, immunological regulation, tumor development, and cell migration 52 - The circulating serum OPN levels are elevated in several cancers, including MM 56 , colon 57 , lung 58 , and breast cancer In particular, Pass et al.

This study showed that there was no significant difference in serum OPN levels between subjects with asbestos exposure and with no asbestos exposure. However, OPN levels in MM were significantly elevated compared to controls and asbestos-exposed individuals. The performance of serum OPN assay was good with A study comparing serum OPN levels from 96 patients with MM and healthy asbestos-exposed subjects showed that assays based on serum OPN levels displayed good sensitivity and specificity to distinguish MM patients from asbestos-exposed individuals The diagnostic performance of OPN for MM was further investigated in several other studies 63 - 67 with conflicting results.

Some of the discrepancies can be explained by the source of the sample used for the OPN assay. Indeed, two separate studies comparing serum and plasma OPN revealed that the diagnostic performance of the OPN assay was higher when performed in plasma than in serum 65 , 68 , because of the lower stability of serum OPN caused by thrombin cleavage during the coagulation process, which may yield unreliable results 62 ,