Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0699790 (colon cancer)
 28,837 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Prostaglandins (PGs) with antiproliferative activity against tumor cells consist of the cyclopentenone PGs and the alkylidene cyclopentenone PGs. Such PGs are PGD2, PGJ2, delta 12-PGJ2, PGA1, delta 7-PGA1, and PGA2. Both PGJ2 and delta 12-PGJ2 are ultimate metabolites of PGD2 and have potent antiproliferative activity on tumor cells. delta 12-PGJ2 was identified in human urine, whereas delta 7-PGA1 has not been found in the human body. One important characteristic of both delta 7-PGA1 and delta 12-PGJ2 is that they have little cross resistance with cisplatin and adriamycin in vitro and in vivo. delta 7-PGA1 has 5-fold greater antitumor activity than delta 12-PGJ2. Methyl ester-delta 7PGA1 (methyl-delta 7-PGA1) is stable chemically and can be easily synthesized in large amounts. All four isomers of methyl-delta 7-PGA1 showed the same antiproliferative activities on ovarian carcinoma cells. In addition, methyl-delta 7-PGA1 integrated in lipid microspheres (lipo-methyl-delta 7-PGA1) is more soluble in water than methyl-delta 7-PGA1 alone. Hence, lipo-methyl-delta 7-PGA1 was selected for extensive preclinical studies. Intravenous administration of lipo-methyl-delta 7-PGA1 could inhibit the growth of both HeLa S3 and Lovo colon cancer cells transplanted subcutaneously in nude mice. Lipo-methyl-delta 7-PGA1 by intraperitoneal administration could prolong the survival of scid mice bearing 2008C/13* cells resistant to cisplatin. The combined administration of cisplatin and lipo-methyl-delta 7-PGA1 prolonged the survival of nude mice bearing HRA cells compared with each single agent alone.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Prostaglandins in the treatment of cancer. 804 95

The human colorectal epithelium is maintained by multipotent stem cells that give rise to absorptive, mucous, and endocrine lineages. Recent evidence suggests that human colorectal cancers are likewise maintained by a minority population of so-called cancer stem cells. We have previously established a human colorectal cancer cell line with multipotent characteristics (HRA-19) and developed a serum-free medium that induces endocrine, mucous and absorptive lineage commitment by HRA-19 cells in vitro. In this study, we investigate the role of the beta1 integrin family of cell surface extracellular matrix receptors in multilineage differentiation by these multipotent human colorectal cancer cells. We show that endocrine and mucous lineage commitment is blocked in the presence of function-blocking antibodies to beta1 integrin. Function-blocking antibodies to alpha2 integrin also blocked both HRA-19 endocrine lineage commitment and enterocytic differentiation by Caco-2 human colon cancer cells; both effects being abrogated by the MEK inhibitor, PD98059, suggesting a role for ERK signaling in alpha2-mediated regulation of colorectal cancer cell differentiation. To further explore the role of alpha2 integrin in multilineage differentiation, we established multipotent cells expressing high levels of wild-type alpha2 integrin or a non-signaling chimeric alpha2 integrin. Overexpression of wild-type alpha2 integrin in HRA-19 cells significantly enhanced endocrine and mucous lineage commitment, while cells expressing the non-signaling chimeric alpha2 integrin had negligible ability for either endocrine or mucous lineage commitment. This study indicates that the collagen receptor alpha2beta1 integrin is a regulator of cell fate in human multipotent colorectal cancer cells.
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PMID:Alpha2beta1 integrin regulates lineage commitment in multipotent human colorectal cancer cells. 1866 72