Panoply™ Human CCR3 Knockdown Stable Cell Line

Myeloid-derived suppressor cells (MDSCs) inhibit anti-tumor immunity and promote cancer progression. While the concept of immunosuppressive MDSCs is well established, the mechanisms by which they regulate non-small cell lung cancer (NSCLC) progression through paracrine signaling remain unclear. Here, researchers found that MDSC infiltration in NSCLC tissues correlates with cancer progression and is positively associated with the development of patient-derived xenograft models and poor patient prognosis. Intratumoral MDSCs directly promote NSCLC metastasis and overexpress chemokines, including CCL11, that promote NSCLC cell invasion. CCL11 activates the AKT and ERK signaling pathways, promoting NSCLC metastasis through the epithelial-mesenchymal transition (EMT) process. Furthermore, elevated CCL11 expression is associated with poor prognosis in lung cancer and other cancer types. These findings emphasize that MDSCs produce CCL11, which promotes NSCLC metastasis by activating ERK and AKT signaling and inducing EMT, suggesting that the MDSCs-CCL11-ERK/AKT-EMT axis comprises a potential target for the treatment of NSCLC metastasis.

Since CCR3 has been identified as the primary receptor for CCL11 in cancer cells, researchers sought to assess the importance of the CCL11-CCR3 interaction in non-small cell lung cancer (NSCLC) metastasis. Here, they performed gene expression analysis of CCR3 knockdown in A549 cells as well as A549 cells treated with CCL11 using RNA-Seq. The PI3K-AKT and Ras-MAPK-ERK pathways were identified as significantly important pathways in CCL11-treated cells (Figure 1A, C) and CCR3 knockdown cells (Figure 1B, C), respectively. Furthermore, researchers demonstrated elevated phosphorylation of ERK1/2 and AKT in invasive tumors (Figure 1D). ERK and AKT are key switches in upstream signaling that promote cell migration. Together, these results suggest that ERK and AKT signaling are crucial in CCL11-induced NSCLC cell metastasis.

Figure 1. AKT and ERK signaling pathways may be involved in CCL11-mediated NSCLC metastasis. (Lin S, et al., 2021)