The transformation of a healthy cell into a cancerous one often comes with a slew of cellular signaling changes. These changes change both the inside activities of the cell, as well as the environment surrounding it.
Chemokines are a family of signaling proteins secreted by cancer cells to manipulate the micro-environment around it. They usually induce and regulate immune cells' movement, but in cancer, they can attract immature immune cells called macrophages. These macrophages mature into tumor-associated macrophages (TAMs), causing cancer growth rather than fighting it.
Glioblastoma multiforme (GBM) is a type of brain cancer where chemokines play a role in its progression. The chemokines CCL2 and CXCL10 have been identified as tumor-promoting in other studies. In Japan, a team from Tokushima University noted a lack of information on how they affect glioma stem cells (GSCs). These are immature cells that are often resistant to chemotherapies. If treatment is unable to get rid of these cells, there is a high chance a patient will experience recurrence.
The study examined the chemotherapy drug celecoxib to see how it affected the chemokines CXCL10 and CCL2 in glioma stem cells. They theorized that some of celecoxib's anti-cancer effects might be mediated by attacking glioma stem cells in a chemokine-dependent manner.
The team used mouse models implanted with glioma stem cells for the study. Celecoxib treatment showed a strong tumor growth impairment, increasing the treated group's survival significantly over the untreated group. A look into CCL2 and CXCL10 expression showed that celecoxib treated mice had decreased expression of both compared to controls, which also translated into a lower accumulation of tumor-associated macrophages in the tumors. This reduced expression of some of the chemokines was tracked back to the NF-kB transcription pathway's impairment.
This study showed that celecoxib could impair the growth of glioma stem cell tumors in a mouse model. This activity was partly due to its regulation of chemokine signaling by inhibiting the NF-kB transcription pathway and preventing the expression of critical components of CCl2 and CXCl10 signaling. Effective treatment of cancer stem cells is crucial for preventing the recurrence of many types of cancers, and this study furthers our understanding of this path in brain cancer.
The study concludes, "our findings suggest that downregulation of the CCL2/CCR2 and CXCL10/CXCR3 axes via inhibition of the NF-κB pathway in the tumor and the tumor microenvironment might have contributed to the antitumor effects of celecoxib observed in the mouse glioma model. These results warrant further investigation to clarify the therapeutic benefits of celecoxib in humans."