Human Breast Cancer Stem Cells Have Significantly Higher Rate of Clathrin-Independent and Caveolin-Independent Endocytosis than the Differentiated Breast Cancer Cells
Kanagaraj Palaniyandi, Barbara A. Pockaj, Sandra J. Gendler and Xiu-Bao Chang*
Department of Biochemistry and Molecular Biology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, AZ 85259, USA
- *Corresponding Author:
- Xiu-bao Chang
Mayo Clinic College of Medicine
13400 East Shea Boulevard, Scottsdale, AZ 85259, USA
Fax: 1-480- 301-8387
E-mail: [email protected]
Received Date: June 15, 2012; Accepted Date: July 24, 2012; Published Date: July 26, 2012
Citation: Palaniyandi K, Pockaj BA, Gendler SJ, Chang XB (2012) Human Breast Cancer Stem Cells Have Significantly Higher Rate of Clathrin-Independent and Caveolin-Independent Endocytosis than the Differentiated Breast Cancer Cells. J Cancer Sci Ther 4: 214-222. doi: 10.4172/1948-5956.1000144
Copyright: © 2012 Palaniyandi K, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.
Breast Cancer Stem (BCS) cells play critical roles in self-renewal, Multi Drug Resistance (MDR), differentiation and generation of secondary tumors. Conventional chemotherapy may efficiently kill the bulk of differentiated drug sensitive breast cancer cells, but not the MDR self-renewable BCS cells, leading to enrichment of the MDR BCS cells. In order to target the MDR BCS cells, we have isolated: 1) BCS cells from either breast cancer cell lines or fresh breast cancer specimens; 2) ATP binding cassette (ABC) transporter group G number 2 (ABCG2)-specific aptamers; and 3) BCS cell-binding aptamers. Interestingly, ABCG2-specific aptamers labeled the membrane surface of the ABCG2-expressing baby hamster kidney (BHK) cells, but stained whole cells of the BCS cells derived from mammospheres, implying that BCS cells might have much higher rate of endocytosis than the ABCG2-expressing BHK cells. In addition, 5D3, a monoclonal antibody that recognizes the extracellular loops of ABCG2 protein, also stained whole BCS cells. Furthermore, BCS cell-binding aptamers stained whole BCS cells, but not the differentiated breast cancer MCF-7 cells. All these results support above conclusion that BCS cells might have high rate of endocytosis. Further experiments performed with aptamers and human transferrin or lactosylceramide showed that BCS cells do have much higher endocytosis rate than the differentiated breast cancer cells. Interestingly, clathrin dependent endocytosis inhibitors, such as monodansylcadaverine or sucrose, or caveolin-dependent endocytosis inhibitors, such as methyl-β-cyclodextrin or genistein, can inhibit the internalization of transferrin or lactosylceramide into the differentiated breast cancer cells, but cannot block the internalization of these compounds into the BCS cells, suggesting that BCS cells undergo clathrin-independent and caveolinindependent endocytosis. Taken together, our data suggest that BCS cells have high rate of endocytosis and open the possibilities for delivering therapeutic agents directly into the MDR BCS cells with aptamer-coated liposomes.