Detection of a pancreatic cancer-associated antigen (DU-PAN-2 antigen) in serum and ascites of patients with adenocarcinoma.

Abstract

A competition radioimmunoassay was developed, utilizing a murine monoclonal antibody to human pancreatic adenocarcinoma cells. Immunoblotting of a standard antigen preparation from either serum or ascites fluid after electrophoresis in 1% agarose showed that the specific DU-PAN-2 activity resided in two major high molecular weight bands. DU-PAN-2 antigen levels were expressed as arbitrary units based on a standard partially purified antigen preparation. The inhibition curve with standard antigen was reproducible (SD < 10%) and essentially linear from 25 to 200 units/ml. The mean DU-PAN-2 antigen concentration for the sera from 126 normal individuals was 81 units/mi. Sera from pediatric patients with malignancy had a mean of 127 units/ml, while nasopharyngeal, stage III melanoma, and ovarian carcinoma patients had means of 89, 92, and 119 units/mi, respectively. All values in normal subjects as well as the melanoma, nasoplaryngeal, ovarian, and pediatric cancer patients were Wiss than 400 units/mi. Intermediate antigen levels were detected in patients with alimentary tract malignancies. Eight of 20 gastric cancer and 8 of 76 colorectal carcinoma patients and 3 patients with benign or nonmalig nant gastrointestinal tract disease had DU-PAN-2 values exceeding 400 units/ml. Ascites fluids from 6/6 and pancreatic juice from 2/2 pancreatic cancer patients had values greater than 750 units/ml. Serum from 68% of the 89 pancreatic cancer patients tested had DU-PAN-2 antigen levels greater than 400 units/ml. The mean serum value in this patient population was 4888 units/mi.

Specific, major histocompatibility complex-unrestricted recognition of tumor-associated mucins by human cytotoxic T cells.

“…It is interesting to speculate that tumor cell production of high levels of circulating mucin, such as is known to occur in pancreatic and breast cancer (21,26), may help tumor cells to escape immune destruction by engaging tumorspecific T-cell clones in the periphery with the soluble antigen.…”

Cystic fibrosis mice lacking Muc1 have reduced amounts of intestinal mucus.

“…Secreted MUC1 is found at high levels in human breast milk and in human bile (12,27). MUC1 has also been detected in serum from patients with breast and pancreatic cancer (10,11) and secreted forms of MUC1 have been shown to exist in tissue culture (13)(14)(15). Mouse cells, when transfected with the full-length MUC1 cDNA, secrete MUC1 protein lacking the cytoplasmic tail into the culture medium (13).…”

“…Muc1 is expressed by most simple secretory epithelia. Although most commonly known as a cell-associated mucin, a secreted form of human MUC1 has been described (10)(11)(12)(13)(14)(15). Muc2, a large secreted mucin, is a goblet cell product that is found mainly in the small intestine and colon (17).…”

“…The core protein consists of an NH 2 -terminal signal sequence, a tandem repeat domain containing numerous serines and threonines, a hydrophobic transmembrane domain, and a cytoplasmic domain (8,9). The existence of a secreted form of MUC1, lacking the cytoplasmic tail, has also been determined (10)(11)(12)(13)(14)(15). In the small intestine and colon, Muc1 is produced at very low levels by enterocytes.…”

Enzyme-linked PNA lectin binding assay compared with CA19-9 and CEA radioimmunoassay as a diagnostic blood test for pancreatic cancer

“…These include carcinoembryonic antigen (CEA) (Gold & Freedman, 1965;Tatsuta et al, 1984), pancreatic oncofetal antigen (POA) (Banwo et al, 1974;Nishida et al, 1985), pancreatic cancer associated antigen (PCAA) (Chu et al, 1977;Loor et al, 1984), (Metzgar et al, 1984;Sawaku et al, 1986), CA19-9 (Koprowski et al, 1979;Haglund et al, 1986b), CA50 (Lindholm et al, 1983;Habib et al, 1986) and CA12-5 (Lehmann et al, 1984;Haglund, 1986). The most successful of these has proved to be CA19-9, which recognises the sialylated blood group Lewis antigen, which is expressed on a mucin secreted by the pancreatic tumour into the serum (Magnani et al, 1983).…”