Bailey, C.; Negus, R.; Peck, D.; Darzi, A.
April 2003
Gut;Apr2003 Supplement 1, Vol. 52, pA94
Academic Journal
The chemokines are a group of more than 40 chemotactic cytokines that are responsible for leukocyte trafficking under normal and pathological conditions. They are small molecules (-70 kDa) that show structural similarities both at the primary and tertiary levels. In particular they are characterised by conserved amino terminal cysteine residues that may be single (C), adjacent (CC) or separated by another amino acid (CXC). Chemokine signalling is mediated via serpentine receptors. Many human tumours contain a leukocyte infiltrate, including colorectal cancer, of which macrophages may form a significant part. In the 1980s and 1990s a variety of tumours were found to express chemokines that may account for the type and distribution of these infiltrates. In particular another epithelial cancer, ovarian, was found to express and produce monocyte chemoattractant protein-1 (MCP-1, CCL2), a potent monocyte/macrophage chemoattractant. MCP-1/CCL2 was expressed predominantly by turnout cells but also by some infiltrating macrophages. We have examined MCP-1/CCL2 production in human colorectal cell lines by specific ELISA and have found constitutive or inducible expression (in response to TNF-α) in 2/3. MCP-1/CCL2 expression has also been examined in RNA extracted from whole tumours and was present in 7/7. In the cell line that did not express MCP-1/CCL2, HT-29, monocyte chemoattractant activity was still present when supernatants were tested using the monocytic cell line THP-1 in Boyden chamber migration assays. We have demonstrated that MCP-1/CCL2 can be produced by colorectal cell lines and is expressed by turnouts. MCP-1/CCL2 may therefore be involved in determining both the type and distribution of the leukocyte infiltrate in these malignancies.


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