In the January 13th edition of Nature Cell Biology, scientists from the Wistar Institute, Q. Huang et al., reported their findings in identifying two microRNAs, miR-373 and miR-520c, involved in metastasis of human breast cancer cells. The invesitgators conducted genetic screening experiments on non-metastatic, human breast tumor cell lines which were transduced with a miRNA expression library. The tranduced cells were subsequently analyzed for their ability to migrate both in vitro and in vivo. The experimental data showed that both miR-373 and miR520c were involved in the inhibition of post-translational tumor suppressor gene expression as well as stimulating cancer cell migration. It also found that endogenous miR373 inversely correlated with upregulation of the adhesion molecule, CD44s. The authors concluded that both miR373 and miR520c may have an important role in modulating tumor migration and invasion which clinically may give rise to metastasis of breast cancer cells.

As a follow-up to yesterday's post on the concept of cancer stem cells, M. Sabatino et al. from National Cancer Institute reported in the January 1st issue of J. Cancer Research the results of their study analyzing genetic instability in human metastatic melanoma cell lines. Using a comparative genomic hybridization (aCGH) assay, the investigators compared gene expression profiles from clonal (autologous) derived cell lines to cell lines originating from other patients. The experimental data showed a strong correlation for core genetic alterations found between the different cell lines with respect to genetic imbalances, global transcriptional patterns, and cellular phenotypes. It was noted that these similarities in genetic instability was not temporal nor did it follow strict temporal progression. The authors noted that their experimental results suggest that conservation of these core genetic alterations supports a cancer stem cell hypothesis. It also pointed out that "genomic imbalances detectable by aCGH contributed only 25% of the transcriptional traits determining autologous tumor distinctiveness."

Cancer biologists are beginning to consider the hypothesis that why many cancer patients relapse may be attributed to cancer stem cells. The cells may be quiescent and extremely difficult to eliminate in a cancer. Based on this premise, W. Matsui et al. from Johns Hopkins University School of Medicine carried out a study to determine if the clonogenic cells in multiple myeloma have properties resembling normal stem cells. The investigators also noted in their research study published in the January 1st issue of J. Cancer Research that these clonogenic cells are drug resistant and arise from a population of CD138^neg B cells. Whereas, the CD138+ cells were sensitive to antimyeloma agents such as dexamethasone, lenadilomide, bortezomib, and 4-hydroxycyclophosaphamide, the CD138^neg cells were not affected by these agents. The researchers reported that the CD138^neg cells stained positive with the Hoechst 34442 for side population stem cells as well as with the Aldefluor assay. The experimental results also showed that the clonogenic cells express the B-cell markers CD20 and CD27. A few of the multiple myeloma cells circulating in the blood stained positive for both Aldefluor and the Hoechst dye. The authors concluded that the ability to efflux the dye may explain, in part, drug resistance in many cancer cells similar to the mechanism that protects normal stem cells from toxic injury.