Disagreement about melanoma CSCs

The Evolving Science of Cancer Stem Cells by Carmen Phillips, NCI Cancer Bulletin 2010(Jul 27); 7(15). Excerpt:

Researchers from Stanford University earlier this month reported in Nature that they had found a marker, CD271, that identified a somewhat unique population of cells that could produce melanoma in highly immunocompromised mice; anywhere from 2.5 percent to 41 percent of cells in their human tumor samples expressed the marker. In additional experiments using similar mice on which human skin was engrafted, only tumor cells with the marker could produce tumors and metastases in the mice. (In his lab, Dr. Morrison noted, the same marker did not differentiate tumor-forming from nontumor-forming cells.)

The publication about CD271 is: Human melanoma-initiating cells express neural crest nerve growth factor receptor CD271 by Alexander D Boiko and 11 colleagues, Nature 2010(Jul 1); 466(7302): 133-7. [PubMed citation].

Comments: The sentence: "In his lab, Dr. Morrison noted, the same marker did not differentiate tumor-forming from nontumor-forming cells" is noteworthy. Why the difference in results for CD271?

The publication by Boiko and co-authors was cited in a previous post to this blog, "Melanoma-initiating cells identified", dated July 1, 2010.

See also an earlier post to this blog, "Tumorigenic cells not rare in human melanoma", dated December 3, 2008.

Targeting tumorogenic cells in neuroblastoma cell lines

Neuroblastoma Cell Lines Contain Pluripotent Tumor Initiating Cells That Are Susceptible to a Targeted Oncolytic Virus by Yonatan Y Mahller and 8 co-authors, including Timothy P Cripe, PLoS ONE 2009; 4(1): e4235 [Epub 2009 Jan 21]. [The full text is openly accessible]. PubMed Abstract:

BACKGROUND: Although disease remission can frequently be achieved for patients with neuroblastoma, relapse is common. The cancer stem cell theory suggests that rare tumorigenic cells, resistant to conventional therapy, are responsible for relapse. If true for neuroblastoma, improved cure rates may only be achieved via identification and therapeutic targeting of the neuroblastoma tumor initiating cell. Based on cues from normal stem cells, evidence for tumor populating progenitor cells has been found in a variety of cancers. METHODOLOGY/PRINCIPAL FINDINGS: Four of eight human neuroblastoma cell lines formed tumorspheres in neural stem cell media, and all contained some cells that expressed neurogenic stem cell markers including CD133, ABCG2, and nestin. Three lines tested could be induced into multi-lineage differentiation. LA-N-5 spheres were further studied and showed a verapamil-sensitive side population, relative resistance to doxorubicin, and CD133+ cells showed increased sphere formation and tumorigenicity. Oncolytic viruses, engineered to be clinically safe by genetic mutation, are emerging as next generation anticancer therapeutics. Because oncolytic viruses circumvent typical drug-resistance mechanisms, they may represent an effective therapy for chemotherapy-resistant tumor initiating cells. A Nestin-targeted oncolytic herpes simplex virus efficiently replicated within and killed neuroblastoma tumor initiating cells preventing their ability to form tumors in athymic nude mice. CONCLUSIONS/SIGNIFICANCE: These results suggest that human neuroblastoma contains tumor initiating cells that may be effectively targeted by an oncolytic virus.

Examples of news items about this publication:

Targeting Cancer's Own Stem Cells to Fight Recurrence, Forbes, January 21, 2009. First paragraph:

Scientists have located a group of cancer stem cells or "tumor-initiating cells" which, when targeted with a reprogrammed herpes virus, are prevented from turning malignant.

Engineered Virus Targets And Kills Apparent Cancer Stem Cells In Neuroblastoma, ScienceDaily, January 21, 2009. First paragraph:

After identifying an apparent population of cancer stem cells for neuroblastoma, researchers successfully used a reprogrammed herpes virus to block tumor formation in mice by targeting and killing the cells.

Virus made to kill cancer stem cells, UPI, January 22, 2009. First paragraph:

U.S. scientists say they have engineered a virus to target and kill apparent cancer stem cells involved in neuroblastoma tumors.

Tumorigenic cells not rare in human melanoma

Efficient tumour formation by single human melanoma cells by Elsa Quintana and 5 co-authors, including Sean J Morrison, Nature 2008(Dec 4); 456(7222): 593-8. Abstract:

A fundamental question in cancer biology is whether cells with tumorigenic potential are common or rare within human cancers. Studies on diverse cancers, including melanoma, have indicated that only rare human cancer cells (0.1–0.0001%) form tumours when transplanted into non-obese diabetic/severe combined immunodeficiency (NOD/SCID) mice. However, the extent to which NOD/SCID mice underestimate the frequency of tumorigenic human cancer cells has been uncertain. Here we show that modified xenotransplantation assay conditions, including the use of more highly immunocompromised NOD/SCID interleukin-2 receptor gamma chain null (Il2rg ^-/-) mice, can increase the detection of tumorigenic melanoma cells by several orders of magnitude. In limiting dilution assays, approximately 25% of unselected melanoma cells from 12 different patients, including cells from primary and metastatic melanomas obtained directly from patients, formed tumours under these more permissive conditions. In single-cell transplants, an average of 27% of unselected melanoma cells from four different patients formed tumours. Modifications to xenotransplantation assays can therefore dramatically increase the detectable frequency of tumorigenic cells, demonstrating that they are common in some human cancers.

See also: U-M scientists probe limits of 'cancer stem-cell model'; Melanoma, the deadliest skin cancer, does not fit the model, News Release, University of Michigan, December 3, 2008.