Primary research

Mammaglobin as a potential molecular target for breast cancer drug delivery

Lian Zuo¹ , Ly Li² , Qian Wang³ , Timothy P Fleming⁴ and Shaojin You⁵

¹  Atlanta Research and Education Foundation, Atlanta VA Medical Center (151), Decatur, GA 30033, USA

²  Department of Chemistry, University of Ningxia School of Chemistry and Chemical Engineering, Yingchuan, Ningxia, PR China

³  Department of Chemistry and Biochemistry, University of South Carolina School of Art and Science, Columbia, SC 29208, USA

⁴  Department of Surgery, Washington University School of Medicine, St. Louis, MO 63110, USA

⁵  Atlanta Research and Education Foundation, Atlanta VA Medical Center (151), Decatur, GA 30033, USA

author email corresponding author email

Cancer Cell International 2009, 9:8doi:10.1186/1475-2867-9-8

Published:	23 March 2009

Abstract

Background

Mammaglobin (MAM) has been used as a specific molecular marker for breast cancer diagnosis. Recently, several groups of researchers proposed a number of therapeutic strategies targeting this molecule. Some of the strategies are based upon an essential but not demonstrated hypothesis – mammaglobin is associated with the surface of breast cancer cells, which strongly disputes the therapeutic strategies.

Results

We conducted a computer-based predictive analysis and identified a small fragment at the N-end of MAM as a potential transmembrane domain. We provided several evidences to demonstrate the presence of the membrane-associated MAM. We isolated the membrane protein components from known MAM positive breast cancer cells (MDA-MB361 and MDA-MB415). We showed that about 22–64% of MAM proteins, depending upon the types of the cancer cells, directly attached on the membrane of breast cancer cells, by Western blotting assays. To directly visualize the presence of the membrane-bound MAM protein, we incubated the MAM positive cancer cells with FITC labeled anti-MAM antibody, and observed clear fluorescent signals on the surface of the cells. In studying the MAM protein distribution in human breast cancer tissues, we first identified two immunostain patterns that are associated with the membrane-bound MAM: the membrane stain pattern and luminary surface stain pattern. To test whether the membrane-associated MAM can serve as a molecular target for drug delivery, we conjugated anti-MAM antibody to human low-density lipoprotein (LDL) and loaded doxorubicin (Dox) in the core of LDL. Specific binding and cytotoxicity of the MAM targeted and Dox loaded LDL was tested in the MAM positive breast cancer cells in vitro.

Conclusion

We first showed that some of MAM protein directly associated with the surface of breast cancer cells. The membrane-associated MAM protein may be utilized as a useful molecular marker for breast cancer targeted drug delivery.