Search PubMed⌕ Search

PubMed · 393609

Acid phosphatase: new developments.

Abstract

Acid phosphatase was the first "tumor marker" to be measured in the blood, and over 40 years have passed since an elevation of the serum acid phosphatase level was observed in patients with prostatic carcinoma. However, significant elevations in the level of this enzyme have been observed in other diseases, as well as elevations of other tissue phosphatases. Many improvements in the colorimetric technique have been introduced, but none has been used successfully to detect the tissue origin of this ubiquitous enzyme. The finding that prostatic acid phosphatase is antigenically distinct from acid phosphatase of other tissues opened a new horizon in the measurement of acid phosphatase in prostatic cancer. On the basis of this immunochemical specificity, several immunoassays have been employed for determining the prostatic acid phosphatase level.

Explore related subjects

Keep this discovery

Explore connections, maps & timelines

BibTeXRIS

N A Romas, N R Rose, M Tannenbaum. 1979. Acid phosphatase: new developments.. https://doi.org/10.1016/s0046-8177(79)80094-5

Cite the original work for its findings. Save a collection to share your selection of sources.

KEEP EXPLORING

Related citations

N-terminal proteolytic processing of porcine chromogranin A in parathyroid tissue.

Chromogranin A (CgA) is a glycoprotein stored in secretory granules of many endocrine and neuroendocrine cells. CgA undergoes tissue specific processing to release regulatory peptides. In the parathyroid, although processing is limited and variable, several CgA-derived peptides have been characterized including parastatin and betagranin. An early stage of CgA processing is the generation of a 64-kDa fragment (CgA64). In this study, we have purified CgA64 from porcine parathyroid glands by chromatographic separations. Edman degradation of this CgA64 yielded the N-terminal sequence NDQAELKEGTEEASSKEAAEKRGDXAVEKND corresponding to pCgA(94-125). Amino acid composition suggests that CgA64 corresponds to CgA(94-430) (i.e. the entire CgA molecule, less the N-terminal residues 1-93). To determine the origin of CgA64, we fractionated parathyroid membrane vesicles by sucrose gradient centrifugation. Intact CgA is predominantly located in dense sucrose fractions (secretory granules), whereas CgA64 is located near the top of the gradient (soluble protein fraction). In vitro incubation of these fractions revealed that the conversion of CgA did not occur in intact granules. These results indicate that CgA64 is not present in intact granules suggesting that it is not a naturally occurring secretory product in parathyroid cells.

Acid Phosphatase↗

Characterization of hK4 (prostase), a prostate-specific serine protease: activation of the precursor of prostate specific antigen (pro-PSA) and single-chain urokinase-type plasminogen activator and degradation of prostatic acid phosphatase.

hK4 (prostase, KLK4), a recently cloned prostate-specific serine protease and a member of the tissue kallikrein family, is a zymogen composed of 228 amino acid residues including an amino-terminal propiece, Ser-Cys-Ser-Gln-. A chimeric form of hK4 (ch-hK4) was constructed in which the propiece of hK4 was replaced by that of prostate-specific antigen (PSA) to create an activation site susceptible to trypsin-type proteases. ch-hK4 was expressed in Escherichia coli, isolated from inclusion bodies, refolded, and purified with an overall yield of 25%. The zymogen was readily self-activated during the refolding process to generate an active form (21 kDa) of hK4 (rhK4). rhK4 cleaved the chromogenic substrates Val-Leu-Arg-pNA (S-2266), Pro-Phe-Arg-pNA (S-2302), Ile-Glu-Gly-Arg-pNA (S-2222), and Val-Leu-Lys-pNA (S-2251), indicating that rhK4 has a trypsin-type substrate specificity. The rhK4 was inhibited by aprotinin (6 kDa), forming an equimolar 27 kDa complex. rhK4 readily activated both the precursor of PSA (pro-PSA) and single chain urokinase-type plasminogen activator (scuPA, pro-uPA). rhK4 also completely degraded prostatic acid phosphatase but failed to cleave serum albumin, another protein purified from human seminal plasma. These results indicate that hK4 may have a role in the physiologic processing of seminal plasma proteins such as pro-PSA, as well as in the pathogenesis of prostate cancer through its activation of pro-uPA.

Acid Phosphatase↗

Dendritic cell-based xenoantigen vaccination for prostate cancer immunotherapy.

Many tumor-associated Ags represent tissue differentiation Ags that are poorly immunogenic. Their weak immunogenicity may be due to immune tolerance to self-Ags. Prostatic acid phosphatase (PAP) is just such an Ag that is expressed by both normal and malignant prostate tissue. We have previously demonstrated that PAP can be immunogenic in a rodent model. However, generation of prostate-specific autoimmunity was seen only when a xenogeneic homolog of PAP was used as the immunogen. To explore the potential role of xenoantigen immunization in cancer patients, we performed a phase I clinical trial using dendritic cells pulsed with recombinant mouse PAP as a tumor vaccine. Twenty-one patients with metastatic prostate cancer received two monthly vaccinations of xenoantigen-loaded dendritic cells with minimal treatment-associated side effects. All patients developed T cell immunity to mouse PAP following immunization. Eleven of the 21 patients also developed T cell proliferative responses to the homologous self-Ag. These responses were associated with Ag-specific IFN-gamma and/or TNF-alpha secretion, but not IL-4, consistent with induction of Th1 immunity. Finally, 6 of 21 patients had clinical stabilization of their previously progressing prostate cancer. All six of these patients developed T cell immunity to human PAP following vaccination. These results demonstrate that xenoantigen immunization can break tolerance to a self-Ag in humans, resulting in a clinically significant antitumor effect.

Acid Phosphatase↗