In the Journal of the National Cancer Institute this week, NCI and NIH researchers present their findings on a study of the effects of brain- and tumor-derived connective tissue growth factor on glioma invasion. CTGF has been previously implicated in cancer metastasis and invasion. For this study, the team harvested highly infiltrative patient-derived glioma tumor-initiating cells and tumor stem cells and analyzed a CTGF-induced signal transduction pathway. It found that treatment of these cells with CTGF resulted in the growth factor binding to ITGB1-TrkA receptor complexes and nuclear factor kappa B transcriptional activation. "TrkA is selectively expressed in the most infiltrative glioma cells in situ and the surrounding reactive astrocytes secrete CTGF," the authors write. "A CTGF-rich microenvironment facilitates CTGF-ITGB1-TrkA complex activation in tumor-initiating cells/tumor stem cells, thereby increasing the invasiveness of malignant gliomas."
Also in the Journal of the National Cancer Institute this week, researchers in the US and Italy explore the modulation of pancreatic cancer chemoresistance through the inhibition of TAK1, a mitogen-activated protein kinase kinase kinase. The researchers measure the activity of nuclear factor κB — which is switched on by TAK1 and promotes chemoresistance — in human pancreatic cancer cells in which TAK1 expression was silenced. "AsPc-1 and MDAPanc-28 TAK1 knockdown cells had a statistically significantly lower NF-κB activity than did their respective control cell lines," the authors write. "The results of this study suggest that genetic silencing or inhibition of TAK1 kinase activity in vivo is a potential therapeutic approach to reversal of the intrinsic chemoresistance of pancreatic cancer."
And finally in the Journal of the National Cancer Institute this week, US researchers write that mammographic breast density can help determine tumor characteristics and subsequent risk of breast cancer in postmenopausal women. The team studied 1,042 postmenopausal women diagnosed with breast cancer and 1,794 matched controls, estimated their breast density from digitized images, and found that the risk of breast cancer increased progressively with increase in percent breast density. "Women with higher breast density [greater than or equal to 50 percent] showed a 3.39-fold increased risk of breast cancer compared with women with lower breast density [less than 10 percent]," the authors write. "The associations between breast density and breast cancer risk were stronger for in situ compared with invasive tumors, high-grade compared with low-grade tumors, larger compared with smaller tumors, and estrogen receptor-negative compared with estrogen receptor-positive tumors."