CSCs responsible for metastasis identified

Cancer stem cells responsible for metastasis identified: HK study, Xinhua News Agency, June 4, 2010. Excerpt:

Hong Kong researchers have identified a subset of cancer stem cells responsible for metastasis in human colorectal cancer which can help better predict the prognosis and design a more suitable treatment for patients, according to a study made public by the University of Hong Kong on Friday.

The researchers from the university's medicine school discovered that cancer stem cells with a surface marker CD26, which marks a subset of cancer stem cells with metastatic capacity, are present in all terminal colon cancer cells and all metastatic cancer cells.

This news item is about the publication: A Subpopulation of CD26+ Cancer Stem Cells with Metastatic Capacity in Human Colorectal Cancer by Roberta Pang and 13 co-authors, including Wai Lun Law, Ronnie T Poon and Benjamin CY Wong [photos of authors], Cell Stem Cell 2010(Jun 4); 6(6): 603-15. [Summary][Twitter entry][Commentary][FriendFeed entry][Science Pond entry].

Aspirin may affect survival of CSC?

Aspirin protection for Lynch syndrome, PhysOrg.com, September 28, 2009. Excerpt:

Professor John Burn, from the Institute of Human Genetics at Newcastle University told the congress ECCO 15 - ESMO 34 held in Berlin on September 21 2009, that he believed that he and his colleagues may have uncovered a simple way of controlling cancer stem cells, which are essential to the formation of malignant tumours.

The clinical trial, which involved 1071 carriers of the Lynch syndrome mutation in 42 centres worldwide, randomised participants to a daily dose of 600mg aspirin and/or 30g Novelose, a resistant starch that escapes digestion in the small intestine.

See also a video (00:11:18) of Prof John Burn, who "talks to ecancer editor Prof Gordon McVie about the results of his trial" (posted September 23, 2009).

And, Aspirin protects against colorectal cancer, says international clinical trial, News Release, ECCO 15 – ESMO 34, September 21, 2009. Excerpt:

The mechanism by which aspirin protects against cancer has yet to be elucidated, but the scientists believe that cancer stem cells are involved.

Also, Aspirin taking on colon cancer, Mark Gertskis, Pharmacy News, September 28, 2009.

Comment: A heads-up: Daily dose of aspirin not safe for everyone, Jodi Mailander Farrell, MiamiHerald.com, September 29, 2009.

CD133 and poorer prognosis in locally advanced colon cancer

Higher percentage of CD133+ cells is associated with poor prognosis in colon carcinoma patients with stage IIIB by Chun-Yan Li and 11 co-authors, including Xiao-Shi Zhang, J Transl Med 2009(Jul 7); 7: 56. [Full text via Libre OA][PMC version of the full text][PubMed Abstract] Final paragraph of the Abstract:

CONCLUSION: The fact that a higher percentage CD133+ cells were strongly associated with a poorer prognosis in patients with locally advanced colon cancer implicated that CD133+ cancer cells contribute to the tumor progression, and the overpopulation hypothesis of cancer stem cell seems reasonable.

CD133 expression has high prognostic impact for colon cancer

The cancer stem cell marker CD133 has high prognostic impact but unknown functional relevance for the metastasis of human colon cancer by David Horst and 6 co-authors, including Thomas Kirchner and Andreas Jung, J Pathol 2009(Jun 25) [Epub ahead of print] PubMed Abstract:

In colon cancer, CD133 has recently been used to enrich for a subset of tumour cells with tumour-initiating capabilities and was therefore suggested to mark colon cancer stem cells. However, this molecule has surprisingly been shown to lack functional importance for tumour initiation itself. Herein, we investigated whether CD133 may be relevant for colon cancer metastasis in patients, and as metastasis requires several additional biological characteristics besides tumour initiation, we examined the effects of knocking down CD133 expression in colon cancer cell lines on proliferation, migration, invasion, and colony formation. We demonstrate that high CD133 expression correlates strongly with synchronous liver metastasis in a matched case-control collection, while siRNA-mediated knock down of this factor has no significant effect on the mentioned biological characteristics. Thus, we conclude that CD133 expression is a marker with high prognostic impact for colon cancer, while it seems to have no obvious functional role as a driving force of this malignancy.

Partnership to develop new colon cancer drugs

Ontario joins top researchers, Pfizer, to develop new colon cancer drugs by Amy Fuller, Canadian Press (via Winnipeg Free Press), July 15, 2009. (See also the same news release, via Yahoo News). First two paragraphs:

The fight against colon cancer got an infusion of funds Wednesday as the Ontario government and leading medical research centres joined with the world's largest pharmaceutical research company to develop new drugs.

Pfizer, a New York-based company with 1,400 employees across Canada, is partnering with the Ontario Cancer Institute and the Ontario Institute for Cancer Research in a $6.9-million collaboration over three years.

See also: Pfizer Gives $5.4M for Ontario Cancer Research Project, GenomeWeb Daily News, July 16, 2009. [Free registration required][Twitter entry]. Excerpts:

Pfizer Global Research and Development will collaborate with two Ontario institutes to discover and validate targets that could be used to diagnose, predict, or treat colorectal cancer.

.....

Ben Neel, who is director of OCI and is serving as a principal investigator on the project, said in a statement that the collaboration will "join the world class genomics and informatics programs at OICR, cutting edge research in cancer stem cell biology and functional genomics at OCI/PMH and the world's largest pharmaceutical company in a concerted effort to bring new therapies to colon cancer patients worldwide."

Single-cell cloning of colon cancer stem cells

Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity by Louis Vermeulen and 8 co-authors, including Jan Paul Medema, Proc Natl Acad Sci USA 2008( Sep 9);105(36): 13427-32. PubMed Abstract:

Colon carcinoma is one of the leading causes of death from cancer and is characterized by a heterogenic pool of cells with distinct differentiation patterns. Recently, it was reported that a population of undifferentiated cells from a primary tumor, so-called cancer stem cells (CSC), can reconstitute the original tumor on xenotransplantation. Here, we show that spheroid cultures of these colon CSCs contain expression of CD133, CD166, CD44, CD29, CD24, Lgr5, and nuclear beta-catenin, which have all been suggested to mark the (cancer) stem cell population. More importantly, by using these spheroid cultures or freshly isolated tumor cells from multiple colon carcinomas, we now provide compelling evidence to indicate that the capacity to propagate a tumor with all differentiated progeny resides in a single CSC. Single-cell-cloned CSCs can form an adenocarcinoma on xenotransplantation but do not generate the stroma within these tumors. Moreover, they can self-renew and are capable of multilineage differentiation. Further analysis indicated that the lineage decision is dictated by phosphoinositide 3-kinase (PI3K) signaling in CSCs. These data support the hypothesis that tumor hierarchy can be traced back to a single CSC that contains multilineage differentiation capacity, and provides clues to the regulation of differentiation in colon cancers in vivo.