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Cell Stem Cell. 2014 Mar 6;14(3):342-56. doi: 10.1016/j.stem.2014.01.009.

CD44v6 is a marker of constitutive and reprogrammed cancer stem cells driving colon cancer metastasis.

Author information

1
Surgical and Oncological Sciences, University of Palermo, 90127 Palermo, Italy; Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, 90127 Palermo, Italy.
2
Surgical and Oncological Sciences, University of Palermo, 90127 Palermo, Italy.
3
Department of Hematology and Oncology, Istituto Superiore di Sanità, 00161 Rome, Italy.
4
Regina Elena National Cancer Institute, 00144 Rome, Italy.
5
Biopathology and Biomedical Methodologies, University of Palermo, 90134 Palermo, Italy; Central Laboratory of Advanced Diagnosis and Biomedical Research (CLADIBIOR), University of Palermo, 90127 Palermo, Italy.
6
Regina Elena National Cancer Institute, 00144 Rome, Italy. Electronic address: demaria@ifo.it.
7
Surgical and Oncological Sciences, University of Palermo, 90127 Palermo, Italy. Electronic address: giorgio.stassi@unipa.it.

Abstract

Cancer stem cells drive tumor formation and metastasis, but how they acquire metastatic traits is not well understood. Here, we show that all colorectal cancer stem cells (CR-CSCs) express CD44v6, which is required for their migration and generation of metastatic tumors. CD44v6 expression is low in primary tumors but demarcated clonogenic CR-CSC populations. Cytokines hepatocyte growth factor (HGF), osteopontin (OPN), and stromal-derived factor 1α (SDF-1), secreted from tumor associated cells, increase CD44v6 expression in CR-CSCs by activating the Wnt/β-catenin pathway, which promotes migration and metastasis. CD44v6(-) progenitor cells do not give rise to metastatic lesions but, when treated with cytokines, acquire CD44v6 expression and metastatic capacity. Importantly, phosphatidylinositol 3-kinase (PI3K) inhibition selectively killed CD44v6 CR-CSCs and reduced metastatic growth. In patient cohorts, low levels of CD44v6 predict increased probability of survival. Thus, the metastatic process in colorectal cancer is initiated by CSCs through the expression of CD44v6, which is both a functional biomarker and therapeutic target.

PMID:
24607406
DOI:
10.1016/j.stem.2014.01.009
[Indexed for MEDLINE]
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