CCL26 participates in the PRL-3-induced promotion of colorectal cancer invasion by stimulating tumor-associated macrophage infiltration

Both phosphatase of regenerating liver-3 (PRL-3) and tumor-associated macrophages (TAMs) influence cancer progression. Whether PRL-3 plays a critical role in colorectal cancer (CRC) invasion and metastasis by inducing TAM infiltration remains unclear. In the present study, we investigated the effects of chemokine ligand 26 (CCL26) on TAM infiltration and CRC invasion and the underlying mechanism in CRC cells by overexpressing or silencing PRL-3. We found that PRL-3 up-regulated CCL26 expression correlatively and participated in cell migration, according to the results of gene ontology analysis. Additionally, immunohistochemistry (IHC) analysis results indicated that the PRL-3 and CCL26 levels were positively correlated and elevated in stage III and IV CRC tissues and were associated with a worse prognosis in CRC patients. Furthermore, we demonstrated that CCL26 induced TAM infiltration by CCL26 binding to the CCR3 receptor. When LoVo-P and HT29-C cells were co-cultured with TAMs, CCL26 binding to the CCR3 receptor enhanced the invasiveness of LoVo-P and HT29-C cells by mobilizing intracellular Ca2+of TAMs to increase the expression of IL-6 and IL-8. Additionally, IHC results indicated that protein levels of CCR3 and TAMs counts were higher in stage III and IV CRC tissues and correlated with CCL26. Moreover, similar results were observed in vivo using mice injected with LoVo-P and HT29-C cells. These data indicate that PRL-3 may represent a potential prognostic marker that promotes CRC invasion and metastasis by up-regulating CCL26 to induce TAM infiltration.

from #ORL-AlexandrosSfakianakis via ola Kala on Inoreader http://ift.tt/2gSJm4u