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

Matilde Todaro, Miriam Gaggianesi, Veronica Catalano, Antonina Benfante, Flora Iovino, Mauro Biffoni, Tiziana Apuzzo, Isabella Sperduti, Silvia Volpe, Gianfranco Cocorullo, Gaspare Gulotta, Francesco Dieli, Ruggero De Maria, and Giorgio Stassi

Cell Stem Cell. 2014; 14(3): 342-56.

Speaker: Wei-Chen Wang (王瑋禎)                                         Time: 14:00~15:00, Oct.29, 2014.

Commentator: Dr. Yao Chang (張堯老師)                           Place: Room 601

Abstract:

Distant metastasis is frequently detected in the colorectal cancer (CRC) patients. The underlying mechanisms of CRC metastasis remain unclear. Cancer stem cell (CSC) has been considered as the progenitor of cancer cell metastases and relapses in cancer patients. It can be identified by the expression of the cell-surface marker [1]. Hermann et al. reported that CSCs may hijack cytokine-regulated migration-signaling pathways to initiate metastasis [2]. However, whether CSCs surface marker play an important role in driving tumorigenesis and result in cancer cell spreading remains unknown. Among the members of the CD44 family of transmembrane glycoproteins, CD44v6 isoforms are involved in the metastatic process [3]. In this study, the authors clarified the mechanism of CD44V6 regulation during colorectal CSCs tumorigenesis and metastasis. Initially, they showed CD44V6 was highly expressed in the metastasis lesion which is required for migration and generation of metastasis tumors. They also found that hepatocyte growth factor (HGF), osteopontin (OPN), and stromal-derived factor 1α (SDF-1) were secreted from the tumor associated cells, which could increase CD44v6 expression and metastasis potential of CSC by activation of the Wnt/β-catenin pathway. Finally, the authors revealed that the PI3K pathway plays an important role in promoting the metastatic activity of CRC cells. Furthermore, inhibition of PI3K pathway in CRC spheres could reduce cell viability and disrupted the expression of cytokine-induced CD44V6. In the clinical study, the authors reported the negative correlation between CD44V6 expression and survival rate of CRC patients (stage III and IV). In conclusion, the authors demonstrate that colorectal CSCs express CD44V6, which is a functional marker and is required for cancer cell metastasis. Above findings were further confirmed in the clinical CRC patients. It suggests that CD44V6 may be a functional biomarker and therapeutic target. 
 

References:

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2.      Hermann PC1, Huber SL, Herrler T, Aicher A, Ellwart JW, Guba M, Bruns CJ, Heeschen C. Distinct populations of cancer stem cells determine tumor growth and metastatic activity in human pancreatic cancer.Cell Stem Cell. 2007; 1(3): 313-23.

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