Introduction of CCR-10

CCR-10, previously known as GPR2, is encoded by the CCR10 gene. It is commonly expressed on melanocytes, plasma cells and memory T-cells (CLA⁺ T lymphocytes), where it functions in T-cell homing to inflamed skin. CCR-10 has been identified as the specific receptor for chemokines SCYA27 (CCL27) and SCYA28 (CCL28), which are a set of small (approximately 8 to 14 kD), structurally related molecules, and modulate cell trafficking of various leukocytes by means of interactions with a subset of seven-transmembrane, G protein-coupled receptors.

Function of CCR-10 Membrane Protein

CCL27 and CCL28 play essential roles in the development, homeostasis, and function of the immune system. And they also have an effect on cells of the central nervous system (CNS) as well as on endothelial cells that participate in angiogenesis or angiostasis. When bond to CCL27, the CCR-10/CCL27 complex plays a role in T cell-mediated skin inflammation. Specifically, CCL27-triggered CCR10 activation has proved to have a positive effect in immune evasion of melanoma cells. They are the most skin-specific chemokine receptor/ligand pair involved in skin allergy and inflammatory diseases. CCL28-associated CCR10 activation may play a role in colonic inflammation. CCR-10 is upregulated together with its ligand CCL28 in myeloid and endothelial cells, during rheumatoid arthritis, which indicates a more common function of activated CCR10 in immune responses and tumor progression. The CCR-10/CCL27 complex is supposed to modulate migration and maintenance of skin T cells, and it is considered as therapeutic targets for treatment of skin diseases.

Application of CCR-10 Membrane Protein in Literature

1. Wu Q., et al. The chemokine receptor CCR10 promotes inflammation-driven hepatocarcinogenesis via PI3K/Akt pathway activation. Cell Death Dis. 2018, 14;9(2): 232. PubMed ID: 29445190

This article suggests that CCL27/CCR10 interaction induces the ERK1/2 pathway, which then increases MMP-7 expression and subsequently promotes breast cancer cell invasion and migration. Thus, CCR10 may be a key regulator in breast cancer cell invasion and migration.

2. Lin H.Y., et al. CCR10 activation stimulates the invasion and migration of breast cancer cells through the ERK1/2/MMP-7 signaling pathway. Int Immunopharmacol. 2017, 51: 124-130. PubMed ID: 28830025

This article shows the promise of CCR10 as a potential therapeutic target for inflammation-driven HCC and reveals that CCR10 seems to function as a linkage between TNF stimulation and downstream PI3K/Akt pathway activation.

3. Hessner F., et al. CC chemokine receptor 10 cell surface presentation in melanocytes is regulated by the novel interaction partner S100A10. Sci Rep. 2016, 6: 22649. PubMed ID: 26941067

Authors in this group identify S100A10 as a novel interaction partner and regulator of CCR10 that might serve as a target for therapeutic intervention and stress the importance of CCR10 function in immune responses and tumor progression.

4. Thangavadivel S., et al. CCR10/CCL27 crosstalk contributes to failure of proteasome-inhibitors in multiple myeloma. Oncotarget. 2016, 7(48): 78605-78618. PubMed ID: 27732933

This article focuses on the treatment strategy for bone marrow-derived chemokines of naive and therapy-refractory myeloma patients. It shows that blocking the CCR10/CCL27/IL-10 myeloma-stroma crosstalk is a novel therapeutic target that could be especially relevant in early refractory myeloma patients.

5. Abeywardane A., et al. N-Arylsulfonyl-α-amino carboxamides are potent and selective inhibitors of the chemokine receptor CCR10 that show efficacy in the murine DNFB model of contact hypersensitivity. Bioorg Med Chem Lett. 2016, 26(21): 5277-5283. PubMed ID: 27692854

This study provides further evidence for the role of CCR10 in dermatological inflammatory conditions.

CCR-10 Preparation Options

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