Baseline CD44v6-positive circulating tumor cells to predict first-line treatment failure in patients with metastatic colorectal cancer.

Chiara Nicolazzo,Flavia Loreni,Rita Zamarchi,Antonella Facchinetti,Paola Gazzaniga,Enrico Cortesi,Elisabetta Rossi,Salvatore Caponnetto,Anna Rita Vestri,Valentina Magri,Angela Gradilone

doi:10.18632/oncotarget.27794

Abstract

CD44v6, the CD44 isoform mostly involved in cancer cell migration and invasion, has been identified as a functional biomarker and therapeutic target in colon cancer stem cells. We here provide evidence that baseline CD44v6-positive CTC predict treatment failure in patients with metastatic colorectal cancer undergoing first-line chemotherapy. We suggest that CD44v6-positive CTC can be used to early detect intrinsic drug resistance in this cancer type.

Highlights

Cellular heterogeneity within circulating tumor cells (CTC) has been widely described and blood-monitoring studies in tumor patients have revealed the presence of CTC able to survive chemotherapy and to generate metastases after xenotransplantation in immunodeficient mice [1]
In order to assess the CD44v6 status in CTC from metastatic colorectal cancer patients, blood samples from 40 patients were analyzed through CellSearch® system before starting first-line therapy
We found a statistical difference between progressive disease and CTC (Fisher’s exact test p = 0.01; PHI index = 0.427 p = 0.007)

Summary

Introduction

Cellular heterogeneity within circulating tumor cells (CTC) has been widely described and blood-monitoring studies in tumor patients have revealed the presence of CTC able to survive chemotherapy and to generate metastases after xenotransplantation in immunodeficient mice [1]. The identification of drug resistant CTC in the entire pool of tumor cells disseminated in the bloodstream would, at least theoretically, provide a unifying hypothesis on CTC and cancer stem cells (CSC). The relationship between circulating tumor cells and cancer stem cells is complex and currently under debate and the discovery of specific markers is an aim hard to be reached [2]. CD44v6 expression has been reported in all colorectal cancer stem cells, and it is required for their migration and generation of metastatic tumors [4]. This concept is supported by experimental mouse models, which demonstrated that tumorigenic activity is confined in the CD44v6 population [3]

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Conclusion