In Cancer Research this week, investigators in the US and Japan report that CCL2 can help to regulate breast cancer stem cells by mediating cross-talk between cancer cells and stromal fibroblasts. When they compared normal fibroblasts to primary cancer-associated fibroblasts and fibroblasts activated by co-cultured breast cancer cells, the researchers found that the latter two produce higher levels of CCL2, which stimulates stem cell-specific, sphere-forming phenotype in breast cancer cells, and the renewal of cancer stem cells. "Increased CCL2 expression in activated fibroblasts required STAT3 activation by diverse breast cancer-secreted cytokines, and in turn, induced Notch1 expression and the [cancer stem cell] features in breast cancer cells, constituting a cancer-stroma-cancer signaling circuit," the team says. In a xenograft model, they observed that loss of CCL2 significantly inhibited tumorigenesis and Notch1 expression. "In addition, upregulation of both Notch1 and CCL2 was associated with poor differentiation in primary breast cancers, further supporting the observation that Notch1 is regulated by CCL2," they add.
Also in Cancer Research, a team of Spanish researchers reports that high expression of IL-13 receptor α2 is associated with invasion, liver metastasis, and poor prognosis in colorectal cancer patients. The team analyzed the secretomes of poorly and highly metastatic colorectal cancer cells and found that highly metastatic cells expressed high levels of IL-4 and IL-13 as well as of IL-13Rα2. "Silencing of IL-13Rα2 in highly metastatic cells led to a decrease in adhesion capacity in vitro and a reduction in liver homing and increased survival in vivo, revealing a role for this receptor in cell adhesion, migration, invasion, and metastatic colonization," the authors write. They also found that high expression of IL-13Rα2 was associated with later stages of disease progression and poor outcome in colorectal cancer patients.
Finally in Cancer Research, researchers in Texas report that the helicase DNA2 alleviates replication stress by promoting DNA end resection. In precancerous and cancerous lesions, growth signals from oncogenes lead to intensive replication stress, which shows itself through a high level of replication-associated DNA double-strand breaks, the authors write. In this study, they found that DNA2 "facilitates homologous recombination to repair replication-associated DNA DSBs," and confers a survival advantage to cells undergoing replication stress. "The nuclease activity of DNA2 was required for DSB end resection, which allowed subsequent recruitment of RPA and RAD51 to repair DSBs and restart replication," the team writes. "More importantly, DNA2 expression was significantly increased in human cancers and its expression correlated with patient outcome."