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  • Little is known about the role

    2021-09-17

    Little is known about the role of GPR35 in physiology and pathology. Using GPR35 knockout and wild-type mice showed that GPR35 activation by KYNA improves energy metabolism and inflammation, while demonstrated that GPR35 plays an important role in the development of angiotensin II-induced hypertension and impaired cardiac function. The participation of GPR35 in pain perception was postulated based on antinociceptive action of its agonists, KYNA and zaprinast (). GPR35 was shown to be a target for common asthma drugs – cromolyn and nedocromil, and thus it was suggested to play an important role in mast cell biology (). In fact, a high quantity of GPR35 is expressed in human mast cells, human basophils and human eosinophils (). Functionally, it has been demonstrated that GPR35 mRNA is upregulated when challenged with IgE etretinate receptor (). However, the significance of GPR35 to asthma and allergy or release of mast cell mediators is yet to be elucidated (). Interestingly, cromolyn and nedocromil are effectively used as eye drops for treating allergic conjunctivitis (). Another GPR35 agonist, lodoxamide (), is indicated for the treatment of vernal keratoconjunctivitis, allergic conjunctivitis, atopic keratitis and superior limbic keratoconjunctivitis (; ; ). Although all these drugs are not selective for GPR35, part of their eye-related biological activity may be mediated by GPR35, especially when their presence in the human cornea and conjunctiva is demonstrated. Further studies are needed to elucidate the role of GPR35 in the therapeutic action of cromolyn, nedocromil, lodoxamide and other GPR35 agonists.
    Introduction Breast cancer is the most common cancer in women. Recently published statistics claim that breast cancer alone is expected to account for 30% of all new cancer diagnoses in women [1]. As is the case in other countries, breast cancer is also the most common cancer in Chinese women. Furthermore, its incidence rate in China has been increasing rapidly in recent years [2]. Therefore, efforts to explore its cause and to create new therapies are of utmost importance. Chemokines are a group of small chemotactic cytokines. They belong to a large chemokine superfamily that consists of, not only a large number of ligands, but also many receptors, including some atypical chemokine receptors. Interactions between chemokines and their receptors have extensive and complex effects on cancer. These effects may act as cancer suppressors through activating and attracting immunologic effector cells or inhibiting tumor angiogenesis, such as CXCL9 (Mig), CXCL10 (IP-10), XCL1 (Ltn), CCL16 (LEC) and CCL19 (ELC). Other effects may promote tumor cell growth or tumor angiogenesis by chemotactic function, thereby promoting cancer progression, such as CXCL8 (IL-8), CCL2 (MCP-1, MCAF), CCL5 (RANTES), CXCL12-CXCR4 and CCL19/21-CCR7 biological axis [3], [4]. Chemokines are also found to play a vital role in the development of breast cancer. For example, CXCR4 and CCR7 are expressed in breast cancer cells, and have been found to metastasize target organs with high expressions of their ligands (CXCL12 and CCL21) [5]. CXCL17 is a new member of the CXC chemokine family that was identified in 2006 by two groups of researchers using different methods. The first group discovered that chemokine was associated with VEGF, and subsequently named it as VEGF-correlated chemokine 1 (VCC-1), which was later certified as CXCL17 [6]. The second group used fold recognition methods to identify this new chemokine, and discovered that it can attract dendritic cells and monocytes [7]. A wider range of research has also studied the function of CXCL17. For example, CXCL17 was found to play a significant role in angiogenesis by promoting the growth of several types of solid tumor cells, such as hepatocellular carcinoma and colon cancer [8], [9], [6], [10], [11]. On the other hand, CXCL17 was found to be associated with a potential anti-tumor immune response in pancreatic cancer [12]. In broader terms, CXCL17 was also found to have anti-microbial and anti-inflammation functions [13], [14].