A New Proteolipid Apparently Associated with Cancer

Skipski, Vladimir P.; Barclay, Marion; Archibald, F. M.; Lynch, Theresa; Stock, C. Chester

doi:10.3181/00379727-136-35471

Cited by 14 publications

(10 citation statements)

References 6 publications

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“…In contrast, tissue markers such as casein (23), a-lactalbumin (24), glycosyltransferases (25), glycolipids (26), and phospholipids (27) have been detected in plasma by a variety of techniques, but none has gained acceptance as a breast cancer marker. Human mammary epithelial antigens detected by MAbs prepared against human milk fat globules have been shown to be elevated in sera of patients with disseminated breast cancer (28).…”

Section: Discussionmentioning

confidence: 99%

Use of a murine monoclonal antibody for detection of circulating plasma DF3 antigen levels in breast cancer patients.

Hayes¹,

Shinmoto²,

Ohno³

et al. 1985

J. Clin. Invest.

192

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The murine monoclonal antibody (MAb), designated DF3, reacts with a 300,000-mol wt mammary epithelial antigen. A sequential double-determinant radioimmunoassay (RIA) has been developed to monitor circulating DF3 antigen. Using this assay, we have demonstrated that 33 of 36 normal women had plasma RIA antigen levels < 150 U/mi. In contrast, 33 of 43 patients (76%) with metastatic breast cancer had RIA DF3 antigen levels _ 150 U/ml. The difference between these two groups was statistically significant (P < 0.001). Similar results have been obtained with a double-determinant enzyme-linked immunoassay (EIA). Only 6 of 111 age-matched normal subjects had EIA DF3 antigens levels _ 30 U/ml, while 42 of 58 patients (72%) with breast cancer had levels equal to or above this value. Thus, similar patterns of specificity are obtained with the EIA or RIA. The elevation of circulating DF3 antigen levels in breast cancer patients has been confirmed by transfer blot assays. MAb DF3 reactivity occurred predominantly with circulating antigens of three different molecular weights ranging from 300,000 to -400,000 mol wt. We also demonstrate that patients with both primary and metastatic breast cancer who were free of detectable disease at the time of sampling have DF3 antigen levels that are similar to those obtained from normal subjects. While patients with hepatoma (27%) and ovarian carcinoma (47%) also had elevated circulating DF3 antigen levels, the results suggest that DF3 antigen levels may be useful in distinguishing breast cancer patients from those with esophageal, gastric, colorectal, pancreatic, and lung carcinomas. Furthermore, the results of the RIA, EIA, and transblot analyses demonstrate that the measurement of circulating DF3 antigen levels provides a new and potentially useful marker to follow the clinical course of patients with metastatic breast cancer.

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Section: Discussionmentioning

confidence: 99%

Use of a murine monoclonal antibody for detection of circulating plasma DF3 antigen levels in breast cancer patients.

Hayes¹,

Shinmoto²,

Ohno³

et al. 1985

J. Clin. Invest.

192

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“…Breast tissue markers such as casein (1) and a-lactalbumin (2) and purported cancer markers such as glycosyltransferases (3,4), glycolipids (5), and phospholipids (6) have been measured in the circulation by a variety of methodologies, but to date none of them has gained widespread acceptance as a breast cancer marker. The markers with high specificity such as casein and a-lactalbumin (which rely for their synthesis on appropriate levels ofhormonal stimulation) are expressed in few tumors and cancer markers such as glycosyltransferases and phospholipids lack specificity for breast (7,8).…”

mentioning

confidence: 99%

Circulating human mammary epithelial antigens in breast cancer.

Ceriani¹,

Sasaki²,

Sussman³

et al. 1982

Proc. Natl. Acad. Sci. U.S.A.

100

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Heterologous specific antisera against human mammary epithelial antigens (HME-Ags), which are present in the human milk fat globule membrane and breast epithelial cells, were used in a solid-phase radioimmunoassay to determine the presence of these antigens in the sera of patients with disseminated cancer of the breast and other organs. Breast cancer patients carry high levels of HME-Ags in their circulation, while patients with disseminated nonbreast cancer, as well as normal female controls, do not. A similar release of HME-Ags in the circulation was shown by us in a model system. To further corroborate these findings, a three-step procedure for the extraction and identification of HME-Ags from the sera was devised. In this analytical procedure, circulating HME-Ags are recovered on a solid phase carrying their corresponding antibody (anti-HME) and radioiodinated in situ. Later, the labeled HME-Ags are released from the solid phase and characterized by NaDodSO4 gel electrophoresis. With this procedure, HME-Ags were isolated from sera of breast cancer patients but not from sera of nonbreast cancer patients or of normal female controls. The extracted HME-Ags had molecular masses of 150,000, 70,000, and 46,000 daltons. To further support these findings, a monoclonal antibody, BLMRL-HMFG-Mc3, directed to the 46,000-dalton HME-Ag was also used to extract its corresponding antigen from sera. Breast cancer patient sera contained such antigen while the sera of the other patients and controls did not. This highly sensitive methodology offers a specific approach to breast cancer diagnosis as well as further insight into the nature ofcirculating antigens with a view to increasing our understanding of breast cancer biology.Early detection and follow-up of breast cancer by noninvasive methodology has been the aim of many studies. Breast tissue markers such as casein (1) and a-lactalbumin (2) and purported cancer markers such as glycosyltransferases (3, 4), glycolipids (5), and phospholipids (6) have been measured in the circulation by a variety of methodologies, but to date none of them has gained widespread acceptance as a breast cancer marker. The markers with high specificity such as casein and a-lactalbumin (which rely for their synthesis on appropriate levels ofhormonal stimulation) are expressed in few tumors and cancer markers such as glycosyltransferases and phospholipids lack specificity for breast (7,8). In view of this, we propose, the use of human mammary epithelial antigens (HME-Ags) as high-prevalence specific markers for breast cancer. HME-Ags are detected by antibodies prepared against the human milk fat globule (HMFG) membrane (9). This membrane is derived from the apical membrane of breast epithelial cells during the process of milk secretion and envelops the fat of milk. HME-Ags are considered cell surface differentiation antigens localized in breast epithelial plasma membrane (9), be these cells normal, neoplastic, fibroadenomatous, displastic, or obtained from male gynecomastias (10). The prese...

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“…These long-chain fatty acids have been reported to be components of proteolipids (Skipski et al, 1971) and of phospholipids in plasma membranes (van Hoeven et at., 1975).…”

Section: Age Lnolmentioning

confidence: 99%

Effect of dietary stearic acid on the genesis of spontaneous mammary adenocarcinomas in strain A/ST mice

Bennett

1984

Intl Journal of Cancer

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Strain A/ST female mice maintained on a high fat (15%) diet in which stearic acid was the major lipid component developed initial spontaneous mammary adenocarcinomas at an older age than mice fed a low fat (4.5%) stock diet. Mice placed on the SA diet at weaning developed tumors at 15.7 +/- 0.87 months compared to 12.7 +/- 0.43 months for those retained on the stock diet (p less than .05). Placing mice on the SA diet at 11.5 months resulted in a smaller but significant increase in the latency period (5.0 +/- 0.86 vs 3.0 +/- 0.57 months +/- 0.57 mo), (p less than .05). Fatty acid analyses of non-tumorous mammary tissue from mid-pregnant mice and of tumor tissues showed that feeding large amounts of 18:0 did not result in increases in the proportion of 18:0. Significant reductions in the percentages of polyunsaturated fatty acids (PUFA) was found in tissues on mice fed the SA diet. The percentage of 18:2 was reduced in both types of tissues; 20:3 and 20:4 was reduced in tumor tissues. Distribution of C18 fatty acids in plasma membranes of tumors of mice fed the two diets were similar; percentages 18:2 was higher in plasma membranes of non-tumorous tissues of mice fed the SA diet. These results suggest that dietary stearic acid interferes with the availability of certain PUFA required for tumor production.

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A New Proteolipid Apparently Associated with Cancer

Cited by 14 publications

References 6 publications

Use of a murine monoclonal antibody for detection of circulating plasma DF3 antigen levels in breast cancer patients.

Use of a murine monoclonal antibody for detection of circulating plasma DF3 antigen levels in breast cancer patients.

Circulating human mammary epithelial antigens in breast cancer.

Effect of dietary stearic acid on the genesis of spontaneous mammary adenocarcinomas in strain A/ST mice

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