Details

Autor(en) / Beteiligte

• Vermeulen, L
• Todaro, M
• de Sousa Mello, F
• Sprick, M.R
• Kemper, K
• Perez Alea, M
• Richel, D.J
• Stassi, G
• Medema, J.P

Titel

Single-cell cloning of colon cancer stem cells reveals a multi-lineage differentiation capacity

Ist Teil von

• Proceedings of the National Academy of Sciences - PNAS, 2008-09, Vol.105 (36), p.13427-13432

Ort / Verlag

United States: National Academy of Sciences

Erscheinungsjahr

2008

Quelle

MEDLINE

Beschreibungen/Notizen

• 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 β-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.