Ccl5, also known as RANTES (regulated on activation, normal T cell expressed and secreted), is a proinflammatory CC subfamily chemokine synthesized by T lymphocytes. It plays a role in immune regulation, being involved in processes such as cell migration and recruitment of immune cells. It may participate in multiple pathways related to inflammation and cancer-related events [3].

In various disease conditions, Ccl5 has been shown to have significant impacts. In pancreatic cancer, scRNA-seq analysis found CCL5-SDC1/4 receptor-ligand interactions between T cells and tumor cells, and CCL5 promoted tumor cell migration in vitro [1]. In glioma, CCL5 from glioma-associated microglia/macrophages regulated glioma migration and invasion via calcium-dependent matrix metalloproteinase 2 [2]. In chordoma, chordoma-secreted CCL5 promoted malignancy progression, macrophage recruitment, and M2 polarization, and CCL5 knockdown inhibited chordoma malignant progression [5]. In renal cancer, CCL5 promoted the epithelial-mesenchymal transition of circulating tumor cells through smad2/3, enhancing the malignant phenotype and facilitating lung metastasis [6]. However, in osteoarthritis, mice lacking CCL5 or CCR5 were not protected against OA, indicating that CCL5/CCR5 may not mediate monocyte recruitment, inflammation, and cartilage destruction in this disease [4].

In conclusion, Ccl5 is a crucial chemokine involved in immune-related processes and has a significant impact on the progression of several cancers, such as pancreatic, glioma, chordoma, and renal cancer. Its role in diseases like osteoarthritis seems to be different. The study of Ccl5, especially through gene knockout models in mouse studies, helps to understand its function in specific biological processes and disease conditions, providing potential therapeutic targets for these diseases.

References:

1. Chen, Kai, Wang, Yazhou, Hou, Yuting, Tian, Xiaodong, Yang, Yinmo. 2022. Single cell RNA-seq reveals the CCL5/SDC1 receptor-ligand interaction between T cells and tumor cells in pancreatic cancer. In Cancer letters, 545, 215834. doi:10.1016/j.canlet.2022.215834. https://pubmed.ncbi.nlm.nih.gov/35917973/

2. Yu-Ju Wu, Caren, Chen, Chia-Hua, Lin, Chun-Yen, Fang, Jia-You, Chen, Pin-Yuan. . CCL5 of glioma-associated microglia/macrophages regulates glioma migration and invasion via calcium-dependent matrix metalloproteinase 2. In Neuro-oncology, 22, 253-266. doi:10.1093/neuonc/noz189. https://pubmed.ncbi.nlm.nih.gov/31593589/

3. Barczak, Katarzyna, Droździk, Agnieszka, Bosiacki, Mateusz, Uriciuc, Willi Andrei, Baranowska-Bosiacka, Irena. 2023. CCL5's Role in Periodontal Disease: A Narrative Review. In International journal of molecular sciences, 24, . doi:10.3390/ijms242417332. https://pubmed.ncbi.nlm.nih.gov/38139161/

4. Raghu, Harini, Lepus, Christin M, Wang, Qian, Sokolove, Jeremy B, Robinson, William H. 2016. CCL2/CCR2, but not CCL5/CCR5, mediates monocyte recruitment, inflammation and cartilage destruction in osteoarthritis. In Annals of the rheumatic diseases, 76, 914-922. doi:10.1136/annrheumdis-2016-210426. https://pubmed.ncbi.nlm.nih.gov/27965260/

5. Xu, Jiuhui, Shi, Qianyu, Lou, Jingbing, Ren, Tingting, Tang, Xiaodong. . Chordoma recruits and polarizes tumor-associated macrophages via secreting CCL5 to promote malignant progression. In Journal for immunotherapy of cancer, 11, . doi:10.1136/jitc-2023-006808. https://pubmed.ncbi.nlm.nih.gov/37185233/

6. Guan, Yibing, Liu, Xueyi, Tian, Juanhua, Gao, Mei, Chong, Tie. 2024. CCL5 promotes the epithelial-mesenchymal transition of circulating tumor cells in renal cancer. In Journal of translational medicine, 22, 817. doi:10.1186/s12967-024-05297-2. https://pubmed.ncbi.nlm.nih.gov/39227943/