CD44v6 Is a Marker of Constitutive and Reprogrammed Cancer Stem Cells Driving Colon Cancer Metastasis

被引：643

作者：

Todaro, Matilde ^{[1
,5
]}

Gaggianesi, Miriam ^{[1
]}

Catalano, Veronica ^{[1
,5
]}

Benfante, Antonina ^{[1
,5
]}

Iovino, Flora ^{[1
]}

Biffoni, Mauro ^{[2
]}

Apuzzo, Tiziana ^{[1
,5
]}

Sperduti, Isabella ^{[3
]}

Volpe, Silvia ^{[1
]}

Cocorullo, Gianfranco ^{[1
]}

Gulotta, Gaspare ^{[1
]}

Dieli, Francesco ^{[4
,5
]}

De Maria, Ruggero ^{[3
]}

Stassi, Giorgio ^{[1
]}

机构：

[1] Univ Palermo, I-90127 Palermo, Italy

[2] Ist Super Sanita, Dept Hematol & Oncol, I-00161 Rome, Italy

[3] Regina Elena Inst Canc Res, I-00144 Rome, Italy

[4] Univ Palermo, I-90134 Palermo, Italy

[5] Univ Palermo, Cent Lab Adv Diag & Biomed Res CLADIBIOR, I-90127 Palermo, Italy

来源：

CELL STEM CELL | 2014年 / 14卷 / 03期

关键词：

COLORECTAL-CANCER; TUMOR-GROWTH; IDENTIFICATION; EXPRESSION; OSTEOPONTIN; RECEPTORS; GENE;

D O I：

10.1016/j.stem.2014.01.009

中图分类号：

Q813 [细胞工程];

学科分类号：

摘要：

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 1 alpha (SDF-1), secreted from tumor associated cells, increase CD44v6 expression in CR-CSCs by activating the Wnt/beta-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.

引用

页码：342 / 356

页数：15

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