Panoply™ Human CXCR1 Knockdown Stable Cell Line

The loss of appropriate cell adhesion normally induces apoptosis via a process termed anoikis. Here, researchers investigated the effects of mesenchymal stem cells (MSCs) within the cancer microenvironment on osteosarcoma (OS) cell resistance to apoptosis and lung metastasis, and evaluated the critical role of the interleukin (IL)-8/C-X-C chemokine receptor (CXCR) 1/Akt signaling pathway in these processes. Metastatic OS subtype cells were isolated from the lung and treated with or without MSC-conditioned medium (MSC-CM) in vitro and designated Saos2-lung-M. Treatment with both MSC-CM and IL-8 enhanced the apoptosis resistance of Saos2 cells in vitro. Furthermore, exogenous MSC-CM promoted the survival and metastasis of Saos2 cells in nude mice. Saos2-lung-M cells were more malignant than their parental cells and were more susceptible to apoptosis. MSC secretion of IL-8 protects OS cells from apoptosis. Blocking the IL-8/CXCR1/Akt pathway by knocking down CXCR1 inhibited lung metastasis of Saos2-lung MSCs and prolonged the survival of tumor-bearing mice. In summary, MSCs enhance the resistance of OS cells to apoptosis and lung metastasis by regulating the IL-8/CXCR1/Akt pathway. These findings suggest that MSCs can "select" OS cells with high metastatic potential in vivo and highlight CXCR1 as a key target in regulating OS cell lung metastasis.

Here, researchers analyzed the in vivo survival of CXCR1-knockdown Saos2-lung-M cells and control Saos2-lung-M cells and found that the survival time of CXCR1-knockdown cells was shorter than that of control cells (Figure 1a, b). Metastatic tumor tissues were collected 4 weeks after injection of CXCR1-knockdown and control Saos2-lung-M cells and immunostained for CXCR1 and p-Akt. HE staining showed that metastatic lymph nodes were smaller, and immunostaining showed that CXCR1 and p-Akt expression was reduced in CXCR1-knockdown mice compared with control mice (Figure 1c, d). These data indicate that CXCR1 knockdown significantly reduced tumor size and metastasis rate and reduced CXCR1/Akt expression (Figure 1e).

Figure 1. Effect of CXCR1 knockdown on OS cell survival in vivo and immunohistochemistry of CXCR1 and p-Akt. (Du L, et al., 2018)