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Proteinase-alpha 2 macroglobulin complexes are not increased in plasma of patients with cancer
S Zucker1, R M Lysik, M H Zarrabi
1Department of Research, Veterans Administration Medical Center, Northport, New York 11768.
Abstract:
Alpha 2-macroglobulin, a major glycoprotein component of plasma, is unique in its capacity to bind and inhibit the proteolytic activities of all classes of proteinases. Since proteinases implicated in cancer dissemination (type-IV collagenase, plasminogen activator, cathepsins B) are normal constitutents of blood, we have explored the hypothesis that elevated tissue levels of activated proteinases bound to alpha 2M might be detected in plasma of patients with cancer. To test this premise, blood was collected from 149 subjects (33 healthy controls, 31 patients with infections and non-malignant diseases, 16 with myeloproliferative disease, 10 with gastrointestinal cancer, 7 with genito-urinary cancer, 16 with lung cancer, 14 with lymphoma, 11 with miscellaneous cancers and 11 with chronic lymphocytic leukemia and myeloma). Plasma was assayed for alpha 2M-proteinase complexes using a sandwich ELISA which employs a mouse monoclonal antibody (MAb) that binds to a neo-antigenic determinant on complexed alpha 2M and a rabbit polyclonal anti-native human alpha 2M antibody. The concentration of complexed alpha 2M in healthy controls was 14.2 +/- 9.8 micrograms/ml (mean +/- standard deviation). No significant differences in complexed alpha 2M were noted between normal and cancer groups (range 7.4-14.6 micrograms/ml). On the basis of these data, we propose that, in patients with cancer, activated proteinases are bound locally to inhibitors in the tissues and are not available to form complexes with plasma alpha 2M. An alternative explanation is that proteinases are not secreted in excess by cancer cells in vivo.
Insights
This study investigated alpha 2-macroglobulin (A2M) proteinase complexes in cancer patients. Results indicate no significant difference in plasma A2M-proteinase complexes between cancer patients and healthy individuals, suggesting localized proteinase inhibition in cancer tissues.
Area of Science:
- Biochemistry
- Oncology
- Immunology
Background:
- Alpha 2-macroglobulin (A2M) is a plasma glycoprotein that inhibits proteinases.
- Proteinases are involved in cancer metastasis, and their presence in plasma was hypothesized to increase A2M complex levels in cancer patients.
Purpose of the Study:
- To investigate the hypothesis that elevated plasma levels of A2M-proteinase complexes are present in cancer patients.
- To determine if plasma A2M-proteinase complex concentrations can serve as a biomarker for cancer.
Main Methods:
- Blood samples were collected from 149 subjects, including healthy controls and patients with various cancers and non-malignant diseases.
- Plasma A2M-proteinase complexes were quantified using a sandwich ELISA with specific monoclonal and polyclonal antibodies.
Main Results:
- The mean concentration of complexed A2M in healthy controls was 14.2 +/- 9.8 micrograms/ml.
- No significant differences in complexed A2M levels were observed between cancer patient groups and healthy controls (range 7.4-14.6 micrograms/ml).
Conclusions:
- The study did not find elevated plasma A2M-proteinase complexes in cancer patients.
- Activated proteinases may be locally inhibited within tumor tissues, preventing their complex formation with plasma A2M.
- Alternatively, cancer cells may not excessively secrete proteinases in vivo.