Mesenchymal Stem/Stromal Cells Exert Trophic Effect on Colorectal Cancer Metastasis to the Liver

Pratika Yuhyi Hernanda ,Alexander Pedroza Gonzalez

doi:10.4172/2167-0889.1000135

Abstract

Colorectal Cancer (CRC) is the third most common cancer in the world. CRC tends to metastasize to the liver, which may occur in 20% to 70% of patients and represents the major cause of death. Mesenchymal Stem/stromal cells (MSCs) have shown to be able to migrate to CRC site and play an important role in tumor progression. We have previously identified a resident MSC population in the liver. Therefore, this study aims to investigate whether there is infiltration of MSCs into patient CRC Liver Metastasis (CRC-LM) and their potential effects on tumor cell growth. By culturing resected patient CRC-LM tissue, we observed the emerging of fibroblast-like cells. Further phenotype and functional characterization confirmed their bonafide MSCs features. In situ staining with a well-established MSCs marker showed a significant enrichment of candidate MSCs in patient CRC-LM, particularly the tumor-stromal area. Moreover, MSCs secreted trophic factors significantly increased colony formation and growth of a metastatic CRC cell line. In summary, we found infiltration and enrichment of MSCs in CRC-LM patient, which could in turn nourish tumor cells.

Highlights

Colorectal Cancer (CRC) is the third most common cancer in the world
Nine paired fresh CRC Liver Metastasis (CRC-LM) and tumor-free liver tissue were collected for Mesenchymal Stem/stromal cells (MSCs) culturing. 12 paraffin-embedded patient CRC-LM tissues were collected at the tissue bank at the Erasmus MC Rotterdam for immunohistochemical staining of MSC marker (Table 1)
To investigate whether MSCs are present in patient CRC-LM tumors, surgical resection of CRC-LM tissues of 9 patients were collected and submitted to an MSC culturing protocol previous validated for liver tissue [14,16]

Summary

Introduction

Colorectal Cancer (CRC) is the third most common cancer in the world. An estimated 1.24 million people worldwide were diagnosed with colorectal cancer in 2008, accounting for 10% of the total cancer patients (http://globocan.iarc.fr/ ). In approximately 75-80% of cases, patients have potentially resectable disease at the time of diagnosis [1]. Liver confined metastases (synchronous metastases) are found in 77% of CRC patients presenting stage IV disease at diagnosis [2]. The treatment of CRC has evolved greatly in the last 10 years, involving complex combined chemotherapy protocols and, in more recent times, new biologic agents. Evidence to date suggests potentially distinct roles for bevacizumab and EGF receptor-targeted biological agents (cetuximab and panitumumab) in the treatment of metastatic CRC. New therapeutic options are urgently needed for advanced or metastatic CRC

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Conclusion