Soluble member(s) of the mesothelin/megakaryocyte potentiating factor family are detectable in sera from patients with ovarian carcinoma

Abstract

ABSTRACTmAb OV569 was made by immunizing mice with ovarian carcinoma cells. It binds to cells from ovarian carcinomas and, to a lesser extent, to cells from certain other carcinomas whereas the binding to normal tissues is low to nondetectable. It also binds to soluble molecule(s) in culture supernatants from antigen-positive carcinomas. OV569 recognizes a protein(s) of 42-45 kDa with the same N-terminal amino acid sequence as the membrane-bound portion of mesothelin and megakaryocyte potentiating factor (MPF). Binding assays with fusion proteins comprising either the N-terminal part of mesothelin͞MPF (D1Ig), reported to be easily cleaved off, or a noncleavable, membrane-associated part (D2Ig) showed that OV569 only binds to D2hIg. A new member of the mesothelin͞MPF family was discovered, which has an 82-bp insert in the membrane-associated part, leading to a frameshift of 212 bp, and whose predicted molecular structure indicates that it is soluble. To test patient sera for soluble tumor antigen, antigen was isolated from cell-free tumor culture supernatants via immunoadsorption with OV569 and used to generate murine mAbs to an epitope different from the one to which OV569 binds, after which mAbs to two different epitopes were used to develop a ''sandwich ELISA.'' Using this assay, the level of circulating antigen was elevated significantly in 23 of 30 sera from patients with ovarian carcinoma, as compared with 0 of 68 sera from healthy controls, 0 of 3 sera from patients with nonneoplastic diseases, and 25 of 75 sera from patients with other tumors. Soluble molecules of the mesothelin͞MPF family may provide useful new marker(s) for diagnosis of ovarian carcinoma and͞or monitoring its response to therapy.

Super pH-sensitive multifunctional polymeric micelle for tumor pHe specific TAT exposure and multidrug resistance

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Label-free, microfluidic separation and enrichment of human breast cancer cells by adhesion difference

“…Current methods for detecting and separating cancer cells rely on observing morphological features or labeling with specific biomarkers. [1][2][3][4][5] Use of a biomarker is highly specific and accurate but requires laborious, time-consuming preparation for staining prior to separation, and a post process such as removal of labeling. Also, a limited number of effective biomarkers (e.g., aptamers 6 ) have been reported for cancer probing and diagnosis.…”

Control of human mesothelin-expressing tumors by DNA vaccines

“…Mesothelin has been found to be highly overexpressed in these intraperitoneal tumors. [11][12][13][14][15] Furthermore, it is absent or present in low levels in normal tissues and other types of cancer. 11 In addition, it has been suggested that mesothelin is a highly immunogenic protein in cancers with high mesothelin expression.…”

“…[11][12][13][14][15] Furthermore, it is absent or present in low levels in normal tissues and other types of cancer. 11 In addition, it has been suggested that mesothelin is a highly immunogenic protein in cancers with high mesothelin expression. For example, Ho et al 16 showed that a high percentage of antimesothelin antibodies was found in ovarian cancer and mesothelioma patient sera and was associated with high expression of the antigen in tumors.…”