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Chemokines are small cytokines or signaling proteins secreted by cells that can induce directed chemotaxis of nearby responding cells. They are classified as C, CC, CXC, or CX3C based on their protein structures. Chemokines can also stimulate other types of migratory behaviors, such as hemizygosity, chemotaxis, and mononuclear chemotaxis, as well as induce cell arrest or adhesion. Chemokines play a crucial role in the migration of immune cells into tumors in cancer, often promoting pro-tumor formation. Additionally, they are involved in various cancer developmental processes, including angiogenesis, metastasis, cancer cell proliferation, stemness, and invasiveness, and are significant determinants of disease progression. Currently, drug development targeting chemokines and their receptors has become a new strategy for cancer treatment.
Figure 1. Human chemokine signaling networks are highly promiscuous. (Sommer F, et al., 2020)
CCL2 is the best-known CC chemokine with chemotactic activity on monocytes and basophils. CCL2 acts through CCR2 to mediate the recruitment of monocytes and macrophages to sites of inflammation. In many cancer types, CCL2 signaling has pro-tumorigenic effects. In patients with breast, prostate, gastric, and ovarian cancers, elevated levels of CCL2 are commonly associated with disease progression. Overexpression of CCL2 or the presence of genetic variants is associated with macrophage recruitment and poor patient prognosis. In addition, CCL2 modulates physiologic bone remodeling in response to hormonal and mechanical stimuli. Studies have shown that CCL2 promotes migration of osteoclast precursor cells and osteoclastogenesis and bone resorption. If the CCL2 and CCR2 genes are mutated, osteoporosis may be induced.
CCL5 is a member of the CC chemokine family, which mainly directs chemotaxis and activation of T lymphocytes and NK cells, and plays an important role in tumors and inflammatory diseases. CCL5 has a role in mediating the directed chemotaxis of immune cells. It enhances the ability of tumor cells to infiltrate and metastasize, which is a major characteristic of the biological behaviors of malignant tumors. Studies have shown that CCL5 serum levels correlate with the stage and disease progression of malignant tumors such as gastric, cervical, and ovarian cancers, and may become a molecular marker for predicting the prognosis of related tumors. In addition, CCL5 secreted by breast cancer cells affects the invasion and metastasis of tumor cells and promotes the formation of neovascularization around tumors after acting on monocytes.
CXCL1 belongs to the CXC chemokine family, mainly expressed in neutrophils and macrophages, with neutrophil chemotactic activity, and plays an important role in inflammation, angiogenesis, and tumorigenesis. CXCL1 expression was elevated in the macrophage-hepatocellular carcinoma microenvironment and was closely associated with the progression and prognosis of hepatocellular carcinoma. In addition, the pathogenesis and inflammatory process of systemic lupus erythematosus (SLE) patients are closely related to CXCL1 serum concentration. Therefore, CXCL1 may become a new target for SLE or cancer therapy.
Creative BioMart is a biotechnology company with GMP proteins as its core business. We are dedicated to providing a range of high-quality GMP-grade chemokines and related customized services to advance scientific research in oncology therapy and targeted drug development. If you are interested in our services or products, please contact us.
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