Cancer Cells with Stem Cell-Like Phenotypes and Liver Metastasis from Colon Carcinoma

Abstract

Tumor heterogeneity contributes to the potentiality of tumors to invade and metastasize. Thus the identification of specific cells programmed to go to a specific site and establish themselves, actively proliferating and causing metastasis, could be fundamental for early diagnosis and for selective targeted therapy. Apart from gene signatures which seem to identify this tumor ability, selected cell populations with self-renewal potential have been recognized: stem cell-like cancer cells. In this paper we review recent evidence on the identification of colon cancer cells with stem cell-like properties which could have a key role in the liver metastasization. The potential clinical implication of their therapeutic eradication is also discussed. Keywords: Stem Cell-Like Cancer cells (SCLC); Colon cancer; MetastasisColorectal Cancer (CRC) is the third most common cancer in men (663,000 cases, 10.0% of the total) and the second in women (570,000 cases, 9.4% of the total) worldwide. Almost 60% of the cases occur in developed regions [1] and approximately 50% of patients develop synchronous or metachronous liver metastases within 2 years from the resection of the primary tumor [2]. Most colon cancer deaths result from the metastatic spread of tumor cells to the liver and other organs [3] and for this reason it is of great significance to identify new markers capable of discriminating earlier the potential that a primary tumor has to initiate a process of liver metastasization. The standard care in patients with operable liver-confined lesions is represented by a combination of chemotherapy and surgery [4]. However, there are still some critical issues to be solved. Firstly, surgical cures are relatively rare in this setting. Secondly, how to juxtapose chemotherapy and surgery, and the duration of chemotherapy. Finally, the possibility of pre-operative chemotherapy in the case of resectable metastases [5]. This is primarily due to the fact that current chemotherapy attacks the bulk of the cancer without affecting the chemo-resistant Stem Cell-Like Cancer cells (SCLCs). These can re-grow after treatment and, eventually, develop the changes responsible for the occurrence of drug-resistance [6][7][8] and facilitate a persistent and aggressive tumor phenotype, capable of invading other sites. In this scenario, understanding what drives metastasization to the liver and the characterization of clonal cells which selectively establish themselves in that site acquires great importance.In CRC, SCLCs are colon stem cells progenitors whose deregulated dynamics lead to the origin of a tumor [9]. At least two populations of progenitors are identified at the bottom of the normal colon Lieberkühn: true quiescent stem cells with high chemoresistance, and low proliferating potential [10]. They produce continuously the second compartment of stem cell progenitors with high mitogenic, differentiation and migratory potentials towards the top epithelium surface of the crypts. Upon migration upward through the crypt, these cells proli...