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Nonspecific suppressive and cytostatic activities mediated by human colonic carcinoma tissue or cultured cell extract
Abstract:
We have previously shown that soluble extracts from human colonic carcinoma (SCE) were potent inhibitors of the PHA-induced DNA synthesis of normal allogeneic peripheral lymphocytes. From the present study, SCE appeared to have a broad and nonspecific range of activity. The SCE-suppressive effect was observed whatever the lymphoid organ or the animal species used as a source of stimulated lymphocytes. Moreover, we always obtained a complete inhibition of the lymphoproliferative response to all tested mitogens including PHA, Con A, PWM, and, for animal lymphocytes, LPS. In addition to the suppressive activity on lymphocytes, SCE also inhibited proliferation of cultured human CCL6 embryonic intestine cells and HT29 colonic carcinoma cells, and of cultured rat fibrosarcoma cells. Soluble extracts from HT29 cells (SCCE) were able to mimic the nonspecific suppressive and cytostatic activities of SCE. The suppressive activity was also found in extracts from hepatic metastases (SHME) of a primary colonic tumor. In contrast, soluble extracts from normal liver or nonmalignant colonic mucosa did not interfere with cell proliferation. These data suggest that both SCE and SCCE contain molecular components(s) that can inhibit a wide variety of proliferating cells, including stimulated lymphocytes.
Insights
Soluble extracts from human colonic carcinoma (SCE) broadly inhibit DNA synthesis in normal lymphocytes and various cancer cells. These extracts, including those from HT29 cells, show potent, nonspecific suppressive and cytostatic activities.
Area of Science:
- Immunology
- Oncology
- Cell Biology
Background:
- Soluble extracts from human colonic carcinoma (SCE) previously demonstrated inhibition of DNA synthesis in normal lymphocytes.
- The broad activity of these extracts requires further investigation.
Purpose of the Study:
- To investigate the range and specificity of the suppressive and cytostatic activities of soluble extracts from human colonic carcinoma.
- To determine if extracts from HT29 cells share similar properties.
Main Methods:
- Testing the effect of SCE on DNA synthesis of lymphocytes from various species and lymphoid organs.
- Evaluating the inhibition of lymphocyte proliferation by multiple mitogens (PHA, Con A, PWM, LPS).
- Assessing the impact of SCE and HT29 cell extracts (SCCE) on the proliferation of human and rat cancer cell lines.
Main Results:
- SCE exhibited broad, nonspecific suppressive activity against stimulated lymphocytes from different species and organs.
- Complete inhibition of lymphoproliferative responses to PHA, Con A, PWM, and LPS was observed.
- SCE and SCCE inhibited proliferation of human intestinal and colonic carcinoma cells, as well as rat fibrosarcoma cells.
- Extracts from hepatic metastases (SHME) showed suppressive activity, unlike extracts from normal tissues.
Conclusions:
- SCE and SCCE contain molecular components that inhibit a wide array of proliferating cells, including stimulated lymphocytes and various cancer cells.
- The suppressive activity is not restricted to lymphocytes and demonstrates a broad cytostatic effect.