Membrane associated cancer-oocyte neoantigen SAS1B/ovastacin is a candidate immunotherapeutic target for uterine tumors.

The metalloproteinase SAS1B [ovastacin, ASTL, astacin-like] was immunolocalized on the oolemma of ovulated human oocytes and in normal ovaries within the pool of growing oocytes where SAS1B protein was restricted to follicular stages spanning the primary-secondary follicle transition through ovulation. Gene-specific PCR and immunohistochemical studies revealed ASTL messages and SAS1B protein in both endometrioid [74%] and malignant mixed Mullerian tumors (MMMT) [87%] of the uterus. A MMMT-derived cell line, SNU539, expressed cell surface SAS1B that, after binding polyclonal antibodies, internalized into EEA1/LAMP1-positive early and late endosomes. Treatment of SNU539 cells with anti-SAS1B polyclonal antibodies caused growth arrest in the presence of active complement. A saporin-immunotoxin directed to SAS1B induced growth arrest and cell death. The oocyte restricted expression pattern of SAS1B among adult organs, cell-surface accessibility, internalization into the endocytic pathway, and tumor cell growth arrest induced by antibody-toxin conjugates suggest therapeutic approaches that would selectively target tumors while limiting adverse drug effects in healthy cells. The SAS1B metalloproteinase is proposed as a prototype cancer-oocyte tumor surface neoantigen for development of targeted immunotherapeutics with limited on-target/off tumor effects predicted to be restricted to the population of growing oocytes.

Sulfatase activity in normal and neoplastic endometrium.

BACKGROUND: Dehydroepiandrosterone sulfate (DHEAS) is metabolized to active androgens and estrogens, which may have a role in the development of endometrial cancer. METHODS: We studied DHEAS conversion to dehydroepiandrosterone (DHEA) in normal and neoplastic endometrium utilizing gas chromatography-mass spectral (GC-MS) analysis. Endometrial homogenate was incubated with known amounts of DHEAS for 4 h at 37 degrees C. Methanol extract was separated from debris by centrifugation, concentrated to 200 microl and 1 microl injected into the GC-MS instrument, equipped with a CP-Sil 8 column. DHEAS and DHEA areas were calculated by autoquantization and DHEA/DHEAS ratio was used for comparing sulfatase activity among normal endometrium (n = 6), Stage I endometrioid carcinoma (EC) (n = 15), Stage I mixed mesodermal Mullerian tumor (MMMT) (n = 6) and Stage I uterine papillary serous carcinoma (UPSC) (n = 7). RESULTS: DHEA/DHEAS ratios in normal endometrium, EC, MMMT and UPSC were 1.45 +/- 1.10, 5.63 +/- 3.27, 2.88 +/- 0.99, and 3.04 +/- 1.76, respectively. Sulfatase activity was significantly higher in EC when compared with normal endometrium (p < 0.001), MMMT (p < 0.05), and UPSC (p < 0.05). The enzyme activity did not differ significantly between low-grade and high-grade EC tumors (5.8 +/- 2.77 and 5.49 +/- 3.84, respectively, p > 0.05). CONCLUSION: Stage I EC have higher sulfatase activity than normal endometrium, and Stage I MMMT and UPSC tumors.