Ccl7

Chemokines, a subgroup of cytokines, are small (size between 8 and 10 kDa), chemotactically active proteins (signal proteins). They are common in all vertebrates, some virus types and bacteria. In humans, about 50 chemokines are currently known.

A strongly conserved structural feature of all chemokines is a fixed group of cysteine residues that is stabilized by 1 or 2 disulfide bridges. This key structural position in the molecule is responsible for its fixed 3-dimensional structure.

In the CC chemokines, the cysteines follow each other directly, in the CXC chemokines they are separated (CC = acronym for cysteine-cysteine) by 1, in the CXXXC chemokines by 3 other amino acids. Chemokines are produced and secreted by a large number of immune cells. They transmit their signals by binding to chemokine receptors via G-proteins. Some chemokines have a pro-inflammatory effect, others have a regulatory effect on the formation, homeostasis and proliferation of tissues.

CCL7 (CC-chemokine ligand 7) is a cytokine of the CC chemokine family. In humans, the chemokine is encoded by the CCL7 gene on chromosome 17q11.2-q12 in a larger cluster adjacent to other chemokine gene loci.

CCL7 is a ligand for the receptors CCR1, CCR2 and CCR3. CCL7 binds to the matrix metalloprotease MMP2. CCL7 has a high homology to CCL2.

CCL7 is formed by monocytes, keratinocytes, endothelial cells, fibroblasts and various tumor cell lines.

CCL7 is formed in psoriatic lesions by keratinocytes and endothelial cells. The chemokine is markedly expressed in lesional psoriatic skin, compared to non-lesional psoriatic skin or to lesional skin in atopic dermatitis or to lichen planus. CCL7 chemokine expression is of considerable importance for the inflammatory response in psoriasis. In animal experiments there is an "upregulation" of the psoriatic key cytokines CCL20, IL-12p40 and IL-17C. Treatment of psoriatics with the TNF-alpha-blocker Infliximab leads to a significant decrease in serum levels of CCL7 within 16 hours, indicating that the chemokine is essential for the maintenance of TNF-alpha-dependent Th1/Th17-mediated inflammation in lesional psoriatic skin (Brunner PM et al. 2015).

CCL7 and CCL21 was overexpressed in the tumor parenchyma of gastric carcinoma (C16.9) and in liver metastases of colorectal carcinoma (C19.-). The intensity of chemokine expression correlated with tumor progression and a poor prognosis.

In oral squamous cell carcinoma (C06.-) CCL7 was also upregulated and was responsible for the invasiveness of the tumor cells, since the invasiveness could be inhibited by a neutralizing CCL7 antibody. In this tumour the chemokine was mainly expressed in "carcinoma-associated fibroblasts (CAF)" (Jung DW et al. 2010).

1. Brunner PM et al (2015) CCL7 contributes to the TNF-alpha-dependent inflammation of lesional psoriatic skin. Exp Dermatol 24:522-528.
2. Cheng JW et al (2014) The role of CXCL12 and CCL7 chemokines in immune regulation, embryonic development, and tissue regeneration. Cytokines 69:277-283.
3. Cho YB et al. (2012) CC chemokine ligand 7 expression in liver metastasis of colorectal cancer. Oncol Rep 28:689-694.
4. Hwang TL et al (2012) CCL7 and CCL21 overexpression in gastric cancer is associated with lymph node metastasis and poor prognosis. World J Gastroenterol 18:1249-1256.
5. Jung DW et al,(2010) Tumor-stromal crosstalk in invasion of oral squamous cell carcinoma: a pivotal role of CCL7. Int J Cancer 127:332-344.
6. Opdenakker G et al (1994): The human MCP-3 gene (SCYA7): cloning, sequence analysis, and assignment to the C-C chemokine gene cluster on chromosomes 17q11.2-q12. genomics 21: 403-408.