Monocyte chemotactic proteins (MCPs) are chemokines involved in macrophage recruitment during inflammation and
cancer invasion . These factors are often produced by invasive cancer cells. Recruitment of
leukocytes to the invasion front and stimulation of the secretion of invasion-promoting proteolytic enzymes from the attracted
leukocytes may contribute to invasion and metastasis of tumor cells
NCBI Summary:
This gene encodes monocyte chemotactic protein 3, a secreted chemokine which attracts macrophages during inflammation and metastasis. It is a member of the C-C subfamily of chemokines which are characterized by having two adjacent cysteine residues. The protein is an in vivo substrate of matrix metalloproteinase 2, an enzyme which degrades components of the extracellular matrix. This gene is part of a cluster of C-C chemokine family members on chromosome 17q.
General function
Ligand, Cytokine
Comment
Cellular localization
Secreted
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Ovarian function
Ovulation
Comment
Kenneth H. H. Wong et al 2002 reported the expression, Hormonal Regulation, and Cyclic Variation of
Chemokines in the Rat Ovary.
A growing body of evidence suggests that mammalian ovulation bears similarities to local inflammatory reactions.
Monocytes/macrophages, eosinophils, and neutrophils are known to infiltrate the area surrounding the dominant follicle
before ovulation. Candidate local chemoattractants may include a family of small cytokines, also known as chemokines. In
the present study, quantitative RT-PCR was used to initially identify and quantify the chemokines expressed in the
preovulatory rat ovary. The chemokines monocyte chemotatic protein 1 (MCP-1), MCP-3, macrophage inflammatory protein
1 (MIP-1), MIP-1? MIP-1, regulated upon activation normal T cell expressed and secreted, eotaxin, interferon-inducible
protein of 10 kDa, growth-regulated oncogene, lymphotactin, and fractalkine were all expressed in the PMSG-primed rat
ovary 6 h post human CG. The cyclic variation of the ovary-positive chemokines was also evaluated throughout the course of a superovulated ovarian
cycle. Significant preovulatory up-regulation relative to the untreated control state was documented for MCP-1 (18-fold), MCP-3 (12-fold), and growth-regulated oncogene (25-fold). In contrast, the preovulatory ovarian expression of eotaxin, fractalkine and regulated upon activation normal T cell expressed and secreted was not increased. These observations
suggest that intraovarian chemokines may be responsible for the cyclic intraovarian residence of representatives of the white
blood cell series.
Expression regulated by
LH
Comment
Ovarian localization
Cumulus
Comment
RhoA/ROCK Signaling in the Cumulus Mediates Extracellular Matrix Assembly. Yodoi R et al. Cumulus cells surround the oocyte and regulate the production and assembly of the extracellular matrix (ECM) around the cumulus-oocyte complex for its timely interaction with sperm in the oviduct. We recently found that C-C chemokines such as CCL2, CCL7 and CCL9 are produced and stimulate integrin-mediated ECM assembly in the post-ovulatory cumulus to protect eggs, and that prostaglandin (PG) E2-EP2 signaling in the cumulus cells facilitates fertilization by suppressing this chemokine signaling, which otherwise results in fertilization failure by preventing sperm penetration through the cumulus ECM. However, it remains unknown as to what mechanisms underlie chemokine-induced cumulus ECM assembly. Here we report that inhibition of EP2 signaling or addition of CCL7 augments RhoA activation and induces the surface accumulation of integrin and the contraction of cumulus cells. Enhanced surface accumulation of integrin then stimulates the formation and assembly of fibronectin fibrils, as well as induces cumulus ECM resistance to hyaluronidase and sperm penetration. These changes in the cumulus ECM as well as cell contraction are relieved by the addition of Y27632 or blebbistatin. These results suggest that chemokines induce integrin engagement to the ECM and consequent ECM remodeling through the RhoA/ROCK/actomyosin pathway, making the cumulus ECM barrier resistant to sperm penetration. Based on these results, we propose that PGE2-EP2 signaling negatively regulates chemokine-induced Rho/ROCK signaling in cumulus cells for successful fertilization.