• Journal of Medicine and Life Science
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• 제15권2호
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• pp.46-50
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• 2018

Cancer, a leading mortality disease following cardiovascular disease worldwide, has high incidence as one out of every four adults in Korea. It was known to be caused by several reasons including somatic mutation, activation of oncogene and chromosome aneuploidy. Cancer cells show a faster growth rate and have metastatic and heterogeneous cell populations compared to normal cells. Cancer stem cells, the most invested field in cancer biology, is a theory to explain heterogeneous cell populations of cancer cells among several characteristics of cancer cells, which is providing the theoretical background for incidence of cancer and treatment failure by drug resistance. Cancer stem cells initially explain heterogeneous cell populations of cancer cells based on the same markers of normal stem cells in cancer, in which only cancer stem cells showed heterogeneity of cancer cells and tumor initiating ability of leukemia. Based on these results, cancer stem cells were reported in various solid cancers such as breast cancer, liver cancer, and lung cancer. Breast cancer stem cells were first reported in solid cancer which had tumor initiating ability and further identified as anti-cancer drug resistance. There were several identification methods in breast cancer stem cells such as specific surface markers and culture methods. The discovery of cancer stem cells not only explains heterogeneity of cancer cells, but it also provides theoretical background for targeting cancer stem cells to complete elimination of cancer cells. Many institutes have been developing new anticancer drugs targeting cancer stem cells, but there have not been noticeable results yet. Many researchers also reported a necessity for improvement of current concepts and methods of research on cancer stem cells. Herein, we discuss the limitations and the perspectives of breast cancer stem cells based on the current concept and history.

• Asian Pacific Journal of Cancer Prevention
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• 제16권17호
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• pp.7491-7496
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• 2015

Background: Biomarkers in breast neoplasms provide invaluable information regarding prognosis and help determining the optimal treatment. We investigated the possible correlation between cancer stem cell (CSC) markers (CD133, and ALDH1) in invasive ductal breast carcinomas with some clinicopathological parameters. Aim: To assess the correlation between expression of cancer stem cell (CSC) markers (CD133, and ALDH1) and clinicopathological parameters of invasive ductal breast carcinomas. Materials and Methods: Immunohistochemical analysis of CD133 and ALDH1 was performed on a series of 120 modified radical mastectomy (MRM) specimens diagnosed as invasive ductal breast carcinoma. Results: Expression of both CD133 and ALDH1 was significantly changed and related to tumor size, tumor stage (TNM), and lymph node metastasis. A negative correlation between CD133 and ALDH1 was found. Conclusions: Detecting the expression of CD133 and ALDH1 in invasive ductal breast carcinomas may be of help in more accurately predicting the aggressive properties and determining the optimal treatment.

• 분석과학
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• 제31권6호
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• pp.232-239
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• 2018

Human breast milk (HBM) provides neonates with indispensable nutrition. The present study evaluated the anti-cancer activity of diluted and pasteurized early HBM (< 6 weeks' lactation) on human breast cancer cell lines. The cell lines MCF7 and MDA-MB231 were exposed to 1 % HBM from the 1st, 3rd, and 6th weeks of lactation and exhibited reduced proliferation rates. As controls, breast cell lines (293T and MCF-10A), breast cancer cell lines (MCF-7 and MDA-MB-231), and $CD133^{hi}CXCR4^{hi}ALDH1^{hi}$ patient-derived human cancer stem-like cells (KU-CSLCs) were treated with prominent milk proteins ${\beta}$-casein, ${\kappa}$-casein, and lactoferrin at varying doses (10, 50, and $100{\mu}g$) for 24 or 48 hrs. The impact of these proteins on cell proliferation was investigated. Breast cancer cell lines treated with ${\kappa}$-casein and lactoferrin exhibited significantly reduced viability, in both a dose- and time-dependent manner. Interestingly, ${\kappa}$-casein selectively impacted only cancer (but not normal breast) cell lines, particularly the more malignant cell line. However, ${\beta}$-casein-exposed human breast cancer cell lines exhibited a significantly higher proliferation rate. Thus, ${\kappa}$-casein and lactoferrin appear to exert selective anti-cancer activities. Further studies are warranted to determine the mechanisms underlying ${\kappa}$-casein- and lactoferrin-mediated cancer cell-selective cytotoxic effects.

• Molecules and Cells
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• 제26권5호
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• pp.514-516
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• 2008

The cancer stem cell hypothesis posits that tumor growth is driven by a rare subpopulation of cells, designated cancer stem cells (CSC). Studies supporting this theory are based in large part on xenotransplantation experiments wherein human cancer cells are grown in immunocompromised mice and only CSC, often constituting less than 1% of the malignancy, generate tumors. Herein, we show that all colonies derived from randomly chosen single cells in mouse lung and breast cancer cell lines form tumors following allografting histocompatible mice. Our study suggests that the majority of malignant cells rather than CSC can sustain tumors and that the cancer stem cell theory must be reevaluated.

• Journal of Ginseng Research
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• 제43권3호
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• pp.421-430
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• 2019

Background: The ginsenoside Rg3, one of active components of red ginseng, has chemopreventive and anticancer potential. Cancer stem cells retain self-renewal properties which account for cancer recurrence and resistance to anticancer therapy. In our present study, we investigated whether the standardized Korean Red Ginseng extract (RGE) and Rg3 could modulate the manifestation of breast cancer stem cell-like features through regulation of self-renewal activity. Methods: The effects of RGE and Rg3 on the proportion of $CD44^{high}/CD24^{low}$ cells, as representative characteristics of stem-like breast cancer cells, were determined by flow cytometry. The mammosphere formation assay was performed to assess self-renewal capacities of breast cancer cells. Aldehyde dehydrogenase activity of MCF-7 mammospheres was measured by the ALDEFLUOR assay. The expression levels of Sox-2, Bmi-1, and P-Akt and the nuclear localization of hypoxia inducible $factor-1{\alpha}$ in MCF-7 mammospheres were verified by immunoblot analysis. Results: Both RGE and Rg3 decreased the viability of breast cancer cells and significantly reduced the populations of $CD44^{high}/CD24^{low}$ in MDA-MB-231 cells. RGE and Rg3 treatment attenuated the expression of Sox-2 and Bmi-1 by inhibiting the nuclear localization of hypoxia inducible $factor-1{\alpha}$ in MCF-7 mammospheres. Suppression of the manifestation of breast cancer stem cell-like properties by Rg3 was mediated through the blockade of Akt-mediated self-renewal signaling. Conclusion: This study suggests that Rg3 has a therapeutic potential targeting breast cancer stem cells.

• 대한의생명과학회지
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• 제27권1호
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• pp.1-11
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• 2021

Cancer stem cells, which are known to drive tumor formation and maintenance, are a major obstacle in the effective treatment of various types of cancer. Trans-membrane glycoprotein mucin 1 antigen and cell surface glycogen CD44 antigen are well-known surface markers of breast cancer cells and breast cancer stem cells, respectively. To effectively treat cancer cells and cancer stem cells, we developed a new drug-encapsulating liposome conjugated with dual-DNA aptamers specific to the surface markers of breast cancer cells and their cancer stem cells. These two aptamer (Apt)-targeted liposomes, which were prepared to encapsulate doxorubicin (Dox), were named "Dual-Apt-Dox". Dual-Apt-Dox is significantly more cytotoxic to both cancer stem cells and cancer cells compared to liposomes lacking the aptamers. Furthermore, we demonstrated the inhibitory efficacy of Dual-Apt-Dox against the experimental lung metastasis of breast cancer stem cells and cancer cells in athymic nude mice. We also showed the potent antitumor effects of dual-aptamer-conjugated liposome systems by targeting cancer cells as well as cancer stem cells. Thus, our data indicate that dual-aptamer-conjugated liposome systems can prove to be effective drug delivery vehicles for breast cancer therapy.

• Molecules and Cells
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• 제43권4호
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• pp.384-396
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• 2020

Breast cancer is one of the most common life-threatening malignancies and the top cause of cancer deaths in women. Although many conventional therapies exist for its treatment, breast cancer still has many handicaps to overcome. Cancer stem cells (CSCs) are a well-known cause of tumor recurrences due to the ability of CSCs for self-renewal and differentiation into cell subpopulations, similar to stem cells. To fully treat breast cancer, a strategy for the treatment of both cancer cells and CSCs is required. However, current strategies for the eradication of CSCs are non-specific and have low efficacy. Therefore, surface biomarkers to selectively treat CSCs need to be developed. Here, 34 out of 641 surface biomarkers on CSCs were identified by proteomic analysis between the human breast adenocarcinoma cell line MCF-7 and MCF-7-derived CSCs. Among them, carcinoembryonic antigen-related cell adhesion molecules 6 (CEACAM6 or CD66c), a member of the CEA family, was selected as a novel biomarker on the CSC surface. This biomarker was then experimentally validated and evaluated for use as a CSC-specific marker. Its biological effects were assessed by treating breast cancer stem cells (BCSCs) with short hairpin (sh)-RNA under oxidative cellular conditions. This study is the first to evaluate the biological function of CD66c as a novel biomarker on the surface of CSCs. This marker is available as a moiety for use in the development of targeted therapeutic agents against CSCs.

• Asian Pacific Journal of Cancer Prevention
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• 제14권5호
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• pp.2789-2800
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• 2013

Background: The aim of this systematic review was to investigate whether stem cells could be effectively applied in targeted therapy of breast cancer. Material and Method: A systematic literature search was performed for original articles published from January 2007 until May 2012. Results: Nine studies met the inclusion criteria for phase I or II clinical trials, of which three used stem cells as vehicles, two trials used autologous hematopoetic stem cells and in four trials cancer stem cells were targeted. Mesenchymal stem cells (MSCs) were applied as cellular vehicles to transfer therapeutic agents. Cell therapy with MSC can successfully target resistant cancers. Cancer stem cells were selectively targeted via a proteasome-dependent suicide gene leading to tumor regression. $Wnt/{\beta}$-catenin signaling pathway has been also evidenced to be an attractive CSC-target. Conclusions: This systematic review focused on two different concepts of stem cells and breast cancer marking a turning point in the trials that applied stem cells as cellular vehicles for targeted delivery therapy as well as CSC-targeted therapies. Applying stem cells as targeted therapy could be an effective therapeutic approach for treatment of breast cancer in the clinic and in therapeutic marketing; however this needs to be confirmed with further clinical investigations.

• Molecules and Cells
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• 제27권4호
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• pp.491-492
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• 2009

We present the result of our research on the tumorigenic ability of single cell clones isolated from an aggressive murine breast cancer cell line in a matched allografting mouse model. Tumor formation is basically dependent on the cell numbers injected per location. We argue that in vivo tumor formation from single cell clones, isolated in vitro from cancer cell lines, may not provide conclusive evidence to disprove the cancer stem cell (CSC) theory without additional data.

• Asian Pacific Journal of Cancer Prevention
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• 제16권3호
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• pp.991-996
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• 2015

Side population (SP) cells have stem cell-like properties with a capacity for self-renewal and are resistant to chemotherapy and radiotherapy. Therefore the presence of SP cells in human breast cancer probably has prognostic value. Objective: To investigate the characteristics of SP cells and identify the relationship between the SP cells levels and clinico-pathological parameters of the breast tumor and disease-free survival (DFS) in breast cancer patients. Materials and Methods: A total of 122 eligible breast cancer patients were consecutively recruited from January 1, 2006 to December 31, 2007 at Yunnan Tumor Hospital. All eligible subjects received conventional treatment and were followed up for seven years. Predictors of recurrence and/or metastasis and DFS were analyzed using Cox regression analysis. Human breast cancer cells were also obtained from fresh human breast cancer tissue and cultured by the nucleic acid dye Hoechst33342 with Verapami. Flow cytometry (FCM) was employed to isolate the cells of SP and non-SP types. Results: In this study, SP cells were identified using flow cytometric analysis with Hoechst 33342 dye efflux. Adjusted for age, tumor size, lymph nodal status, histological grade, the Cox model showed a higher risk of recurrence and/or metastasis positively associated with the SP cell level (1.75, 1.02-2.98), as well as with axillary lymph node metastasis (2.99, 1.76-5.09), pathology invasiveness type (1.7, 1.14-2.55), and tumor volume doubling time (TVDT) (1.54, 1.01-2.36). Conclusions: The SP cell level is independently associated with tumor progression and clinical outcome after controlling for other pathological factors. The axillary lymph node status, TVDT and the status of non-invasive or invasive tumor independently predict the prognosis of breast cancer.