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World J Gastroenterol. Apr 21, 2014; 20(15): 4189-4196
Published online Apr 21, 2014. doi: 10.3748/wjg.v20.i15.4189
Hallmarks in colorectal cancer: Angiogenesis and cancer stem-like cells
Muriel Mathonnet, Aurelie Perraud, Niki Christou, Hussein Akil, Carole Melin, Serge Battu, Marie-Odile Jauberteau, Yves Denizot
Muriel Mathonnet, Aurelie Perraud, Niki Christou, Carole Melin, Department of Digestive Surgery, Limoges University Hospital, 87042 Limoges, France
Muriel Mathonnet, Aurelie Perraud, Hussein Akil, Carole Melin, Serge Battu, Marie-Odile Jauberteau, Homéostasie Cellulaire at Pathologies, Faculty of Medicine, University of Limoges, 87025 Limoges, France
Yves Denizot, Institut 145 GEIST, UMR CNRS 7276, Faculty of Medicine, University of Limoges, 87025 Limoges, France
Author contributions: Mathonnet M, Christou N, Akil H and Battu S analyzed the literature; Perraud A and Mathonnet M wrote the manuscript; Jauberteau MO and Denizot Y revised the manuscript; Melin C contributed to the bibliography.
Supported by Grants from the University of Limoges, Limoges University Hospital, La Ligue Contre le Cancer and the Région Limousin, which was given financial by the Comité Orientation Recherche Cancer (to Perraud A, Christou N and Akil H)
Correspondence to: Muriel Mathonnet, MD, PhD, Professor of Digestive Surgery, Department of Digestive Surgery, Limoges University Hospital, 2 Ave Martin Luther King, 87042 Limoges, France. mathonnet@unilim.fr
Telephone: +33-555-056713 Fax: +33-555-056525
Received: October 3, 2013
Revised: January 26, 2014
Accepted: March 19, 2014
Published online: April 21, 2014
Processing time: 185 Days and 16.3 Hours
Abstract

Carcinogenesis is a multistep process that requires the accumulation of various genetic and epigenetic aberrations to drive the progressive malignant transformation of normal human cells. Two major hallmarks of carcinogenesis that have been described are angiogenesis and the stem cell characteristic of limitless replicative potential. These properties have been targeted over the past decade in the development of therapeutic treatments for colorectal cancer (CRC), one of the most commonly diagnosed and lethal cancers worldwide. The treatment of solid tumor cancers such as CRC has been challenging due to the heterogeneity of the tumor itself and the chemoresistance of the malignant cells. Furthermore, the same microenvironment that maintains the pool of intestinal stem cells that contribute to the continuous renewal of the intestinal epithelia also provides the necessary conditions for proliferative growth of cancer stem-like cells. These cancer stem-like cells are responsible for the resistance to therapy and cancer recurrence, though they represent less than 2.5% of the tumor mass. The stromal environment surrounding the tumor cells, referred to as the tumor niche, also supports angiogenesis, which supplies the oxygen and nutrients needed for tumor development. Anti-angiogenic therapy, such as with bevacizumab, a monoclonal antibody against vascular-endothelial growth factor, significantly prolongs the survival of metastatic CRC patients. However, such treatments are not completely curative, and a large proportion of patient tumors retain chemoresistance or show recurrence. This article reviews the current knowledge regarding the molecular phenotype of CRC cancer cells, as well as discusses the mechanisms contributing to their maintenance. Future personalized therapeutic approaches that are based on the interaction of the carcinogenic hallmarks, namely angiogenic and proliferative attributes, could improve survival and decrease adverse effects induced by unnecessary chemotherapy.

Keywords: Colon cancer; Stem cell; Cancer stem-like cell; Tumor-initiating cell; Microenvironment

Core tip: Recent progress in the therapeutic treatment of colorectal cancer has resulted from targeting the hallmark stem cell-like properties of tumor cells. The survival of colorectal cancer patients has been significantly prolonged with bevacizumab, which inhibits angiogenesis providing the proliferative conditions for tumor cell growth. Personalized therapeutic approaches, centered on the angiogenic and proliferative properties of cancerous cells, could improve patient survival and decrease adverse effects induced by unnecessary chemotherapy.