J. E. Carpentino et al. from the Univ. of Florida reported in the October 6th online edition of Cancer Research their study on the tumorigenicity of aldehyde dehydrogenase (ALDH) expressing epithelial cells from the tissues of patients with chronic ulcerative colitis. With fluorescence-activated cell sorting (FACS), were able to isolate and characterized ALDH expressing cells from the tissues of colitis patients that subsequently formed tumors in xenografts. The investigators were also able to generate spheres in cell cultures. Additionally, the researchers found that the surrounding inflammatory tumor microenvironment determined tumor growth and subsequent metastasis. With colon cancer stem cells (ALDH+), the investigators analyzed their growth rates when they were implanted into mice in conjunction with intestinal stroma cells from normal, colitic and cancerous tissues. ALDH cells paired with stromal cells from normal tissues grew at the slowest rates, whereas, the tumor-initiating cells paired with colitic stromal cells grew at the fastest rate. ALDH cells paired with cancerous tissues grew at an intermediate rate. The experimental data revealed paracrine factors, i.e. IL-6 and IL-8, are upregulated in the inflammatory and malignant stroma and contributes to the tumor growth rates. When the expression of these proinflammatory cytokines were decreased there was a dramatic decrease in tumor growth. The authors concluded that their observations link colitis and cancer (similar to other cancers such as in liver cancers in which chronic inflammation may give rise to hepatic carcinoma).

Scientists from the Univ. of Connecticut School of Medicine, Y. Li et al., noted in their research paper published in the October 8th online edition of Stem Cells, that investigators in the past have attempted to use embryonic and fetal cells as therapeutic anti-cancer vaccines. The use of such cells was based upon the premise that cancer cells expressed oncofetal antigens. It has become clearer that these shared antigens are most likely expressed by the tumor-initiating/cancer stem cells within the tumor. With cell lines of both human embryonic stem cells (hESCs) and induced pluripotent stem (iPS) cells, the scientists conducted a study determining the anti-tumor effect of mice vaccinated with the pluripotent cells. The investigators found that the injected cells generated both a cellular and humoral immune responses against a colon carcinoma (CT26). The experimental data revealed that protection was associated with an increase in the number of cells producing interferon-gamma concomitant with the loss of myeloid suppressor cells (CD11b+Gr-1+). It was also noted that iPS cells were less immunogenic than hESCs in conferring an anti-tumor effect. The data suggest that heterogeneity are found in the expression of oncofetal surface antigens by either iPS cells or hESCs.

Swiss scientists F. Varnat et al. from University of Geneva Medical School published in the September/October issue of EMBO Molecular Medicine the results of their study on correlating Hedgehog-Gli1 (Hh-Gli1) signaling and human colon cancer. The investigators found that epithelial cells and stem cells in human colon carcinomas (CCs) express Gli1, Ptch1, and sonic hedgehog (Shh) in primary and metastatic tissue samples from hCCs. Additionally, increased Hh-Gli1 signaling is associated with tumor progression and mestastasis. It was also found that high Gli1 levels are found in epithelial stem cells (CD133+). The experimental data showed that repression of Hh-Gli1 signaling by RNAi or cyclopamine treatment abrogrates tumor growth in mice. The investigators also reported that Hh-Gli1 signaling is required for CC stem cells to survive in CC xenografts. In vitro results support the researchers' novel tumor cell competition assay that proliferation and self-renewal of CC stem cells are dependent upon Hh-Gli1 activity. The authors concluded that their results "indicate a key and essential role of the Hh-Gli1 pathway in promoting CC growth, stem cell self-renewal and metastatic behavior in advanced cancers."