Publications (3)7.74 Total impact
Article: The Role of Cancer Stem Cells in the Organ Tropism of Breast Cancer Metastasis: A Mechanistic Balance between the "Seed" and the "Soil"?[show abstract] [hide abstract]
ABSTRACT: Breast cancer is a prevalent disease worldwide, and the majority of deaths occur due to metastatic disease. Clinical studies have identified a specific pattern for the metastatic spread of breast cancer, termed organ tropism; where preferential secondary sites include lymph node, bone, brain, lung, and liver. A rare subpopulation of tumor cells, the cancer stem cells (CSCs), has been hypothesized to be responsible for metastatic disease and therapy resistance. Current treatments are highly ineffective against metastatic breast cancer, likely due to the innate therapy resistance of CSCs and the complex interactions that occur between cancer cells and their metastatic microenvironments. A better understanding of these interactions is essential for the development of novel therapeutic targets for metastatic disease. This paper summarizes the characteristics of breast CSCs and their potential metastatic microenvironments. Furthermore, it raises the question of the existence of a CSC niche and highlights areas for future investigation.International journal of breast cancer. 01/2012; 2012:209748.
Article: Recombinant human erythropoietin in combination with chemotherapy increases breast cancer metastasis in preclinical mouse models.[show abstract] [hide abstract]
ABSTRACT: Erythropoiesis-stimulating agents (ESA) are used clinically for treating cancer-related anemia. Recent clinical trials have reported increased adverse events and reduced survival in ESA-treated breast cancer patients receiving chemotherapy, potentially related to erythropoietin (EPO)-induced cancer progression. However, minimal preclinical data are available about the impact of EPO on metastatic cell behavior and/or the metastatic process, and this was the goal of our study. Breast cancer cell lines were treated with recombinant human EPO (rHuEPO) and screened for expression of EPO receptors (EPOR). MDA-MB-231 and MDA-MB-435 cell lines were used for functional assays in vitro (two-dimensional/three-dimensional growth and survival) and in vivo (tumorigenicity and metastasis), in the presence or absence of EPO and/or cytotoxic agents. A large variation in EPOR expression across cell lines was observed. In vitro, rHuEPO had a protective effect on radiation-treated MDA-MB-435 cells (P < 0.05); however, rHuEPO treatment alone or combined with chemotherapy or hypoxia did not influence cell survival. In vivo, rHuEPO increased lung metastases in immunocompromised mice injected with MDA-MB-231 or MDA-MB-435 cells and treated with chemotherapy relative to mice treated with chemotherapy alone (P < 0.05). The lack of an in vitro effect of rHuEPO highlights the importance of in vivo studies to delineate the effects of EPO on the metastatic process. These studies may begin to uncover the underlying functional explanation for the observed EPO-related adverse events and decreased survival in ESA-treated metastatic breast cancer patients undergoing chemotherapy.Clinical Cancer Research 08/2011; 17(19):6151-62. · 7.74 Impact Factor
Chapter: Cancer Stem Cells in Breast Cancer[show abstract] [hide abstract]
ABSTRACT: Breast cancer is one of the leading causes of cancer-related deaths among women worldwide. While it is highly treatable during the primary stages, the disease is often lethal if it successfully metastasizes. Breast cancer stem cells (CSCs) show distinct similarities to normal breast stem cells, have been shown to be the driving force behind primary tumorigenesis, and are postulated to be the cells responsible for metastasis. Many groups have used the CD44+CD24− and/or ALDH+ phenotype for breast CSC isolation; however, this definition does not apply to all breast cancers and needs further refining. As CSCs have been shown to be therapy resistant, identification of additional markers will aid in the isolation of a pure CSC population, which can then be used to elucidate effective treatments. This chapter will discuss normal breast stem cells, breast CSC identification, the relationship between normal mammary stem cells and breast CSCs, and the clinical implications of the CSC population in breast cancer.12/2010: pages 15-36;