Human Breast Cancer Cell Lines Co-Express Neuronal, Epithelial, and Melanocytic Differentiation Markers In Vitro and In Vivo

Qingbei Zhang,Robert M Hoffman,Jikun Shen,Hanli Fan,H Rosie Xing,Syed A Aziz

doi:10.1371/journal.pone.0009712

Abstract

Differentiation programs are aberrant in cancer cells allowing them to express differentiation markers in addition to their tissue of origin. In the present study, we demonstrate the multi-lineage differentiation potential of breast cancer cell lines to express multiple neuronal/glial lineage-specific markers as well as mammary epithelial and melanocytic-specific markers. Multilineage expression was detected in luminal (MCF-7 and SKBR3) and basal (MDA-MB-231) types of human breast cancer cell lines. We also observed comparable co-expression of these three cell lineage markers in MDA-MB-435 cells in vitro, in MDA-MB-435 primary tumors derived from parental and single cell clones and in lung metastases in vivo. Furthermore, ectoderm multi-lineage transdifferentiation was also found in human melanoma (Ul-MeL) and glioblastoma cell lines (U87 and D54). These observations indicate that aberrant multi-lineage transdifferentiation or lineage infidelity may be a wide spread phenomenon in cancer.

Highlights

Cancer diagnosis of the tissue origin of metastatic lesions, especially those from occult primary tumors, relies heavily on the expression of cellular or tissue differentiation markers
A microarray analysis has indicated that the gene expression pattern of the human MDA-MB-435 [4] resembles that of human melanoma cell lines [5]
A recent investigation confirmed the ability of MDA-MB-435 cells to co-express markers of mammary epithelium and melanocytes both in vitro and in vivo, and postulated committing lineage infidelity as an underlying mechanism for the observed dual lineage transdifferentiation [11]

Summary

Introduction

Cancer diagnosis of the tissue origin of metastatic lesions, especially those from occult primary tumors, relies heavily on the expression of cellular or tissue differentiation markers. A recent investigation confirmed the ability of MDA-MB-435 cells to co-express markers of mammary epithelium and melanocytes both in vitro and in vivo, and postulated committing lineage infidelity as an underlying mechanism for the observed dual lineage transdifferentiation [11] Another recent study reported the robust expression of melanocyterelated genes in a variety of breast cancer cell lines including MDAMB-435, and more importantly in freshly resected and histopathologically confirmed human breast cancer specimens [12]. We observed the co-expression of three ectoderm cell lineage markers in other luminal (MCF-7 and SKBR3) and basal (MDA-MB-231) types of human breast cancer cell lines, as well as in human melanoma and glioblastoma cancer cell lines generated from tumors of ectoderm origin These observations indicate that while terminal differentiation to the anticipated cellular type is compromised in the cancerous state, aberrant multi-lineage transdifferentiation or lineage infidelity may be a wide spread in cancer phenomenon

Materials and Methods

Author Contributions