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Cancer stem cells in breast cancer.

Takahashi RU, Takeshita F, Fujiwara T, Ono M, Ochiya T - Cancers (Basel) (2011)

Bottom Line: CSCs share a variety of biological properties with normal somatic stem cells in self-renewal, the propagation of differentiated progeny, the expression of specific cell markers and stem cell genes, and the utilization of common signaling pathways and the stem cell niche.However, CSCs differ from normal stem cells in their chemoresistance and their tumorigenic and metastatic activities.In addition, we especially focus on the CSCs of breast cancer since the use of neoadjuvant chemotherapy can lead to the enrichment of CSCs in patients with that disease.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. tochiya@ncc.go.jp.

ABSTRACT
The cancer stem cell (CSC) theory is generally acknowledged as an important field of cancer research, not only as an academic matter but also as a crucial aspect of clinical practice. CSCs share a variety of biological properties with normal somatic stem cells in self-renewal, the propagation of differentiated progeny, the expression of specific cell markers and stem cell genes, and the utilization of common signaling pathways and the stem cell niche. However, CSCs differ from normal stem cells in their chemoresistance and their tumorigenic and metastatic activities. In this review, we focus on recent reports regarding the identification of CSC markers and the molecular mechanism of CSC phenotypes to understand the basic properties and molecular target of CSCs. In addition, we especially focus on the CSCs of breast cancer since the use of neoadjuvant chemotherapy can lead to the enrichment of CSCs in patients with that disease. The identification of CSC markers and an improved understanding of the molecular mechanism of CSC phenotypes should lead to progress in cancer therapy and improved prognoses for patients with cancer.

No MeSH data available.


Related in: MedlinePlus

miRNA regulates BCSC phenotypes. Let-7 [61], miR-30 [102], and miR-200 [62] may regulate BCSC phenotypes by modulating the expression of their target genes. The expression of let-7, miR-30, and miR-200 is remarkably reduced in BCSCs, progressively increased with the differentiation of BCSCs, and inversely correlated with the expression of their target genes. miR-9 [101], miR-328 [67], miR-373 and miR-520c [103] also regulate BCSC phenotypes.
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f1-cancers-03-01311: miRNA regulates BCSC phenotypes. Let-7 [61], miR-30 [102], and miR-200 [62] may regulate BCSC phenotypes by modulating the expression of their target genes. The expression of let-7, miR-30, and miR-200 is remarkably reduced in BCSCs, progressively increased with the differentiation of BCSCs, and inversely correlated with the expression of their target genes. miR-9 [101], miR-328 [67], miR-373 and miR-520c [103] also regulate BCSC phenotypes.

Mentions: The emergence of miRNAs as important players in breast cancer has led researchers to explore the molecular mechanism that regulates BCSC phenotypes [61-63]. Some miRNAs play important roles in the phenotype formation of BCSCs, and multiple targets of these miRNAs have been identified [95,96] (Figure 1). Let-7 was originally identified in the nematode Caenorhabditis elegans [97,98]. Subsequently, the conservation of the let-7 sequence and its function in mammals were reported. Let-7 was one of the most consistently and significantly reduced miRNAs in many types of tumors, and downreglation of its expression was associated with the progression of tumor malignancy [99]. Recent studies have shown that let-7 suppresses self-renewal in both normal cells and BCSCs. Let-7 also regulates BCSC phenotypes such as chemoresistance and asymmetric cell division [61]. Several oncogenes, including c-Myc, Ras, HMGA2, cyclin D, and IL-6, have been reported as the targets of let-7 [61,63,99]. HMGA2 and Ras are highly expressed in BCSCs and remarkably repressed in non-BCSCs [61]. A comprehensive pathway involved in let-7 and lin-28 promotes the tumor metastasis and BCSC-induced inflammatory response [63]. Lin-28 is a highly specific embryonic stem cell marker and behaves as a negative regulator of let-7. Let-7 also directly represses lin-28 expression in ES and cancer cells [100].


Cancer stem cells in breast cancer.

Takahashi RU, Takeshita F, Fujiwara T, Ono M, Ochiya T - Cancers (Basel) (2011)

miRNA regulates BCSC phenotypes. Let-7 [61], miR-30 [102], and miR-200 [62] may regulate BCSC phenotypes by modulating the expression of their target genes. The expression of let-7, miR-30, and miR-200 is remarkably reduced in BCSCs, progressively increased with the differentiation of BCSCs, and inversely correlated with the expression of their target genes. miR-9 [101], miR-328 [67], miR-373 and miR-520c [103] also regulate BCSC phenotypes.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3756415&req=5

f1-cancers-03-01311: miRNA regulates BCSC phenotypes. Let-7 [61], miR-30 [102], and miR-200 [62] may regulate BCSC phenotypes by modulating the expression of their target genes. The expression of let-7, miR-30, and miR-200 is remarkably reduced in BCSCs, progressively increased with the differentiation of BCSCs, and inversely correlated with the expression of their target genes. miR-9 [101], miR-328 [67], miR-373 and miR-520c [103] also regulate BCSC phenotypes.
Mentions: The emergence of miRNAs as important players in breast cancer has led researchers to explore the molecular mechanism that regulates BCSC phenotypes [61-63]. Some miRNAs play important roles in the phenotype formation of BCSCs, and multiple targets of these miRNAs have been identified [95,96] (Figure 1). Let-7 was originally identified in the nematode Caenorhabditis elegans [97,98]. Subsequently, the conservation of the let-7 sequence and its function in mammals were reported. Let-7 was one of the most consistently and significantly reduced miRNAs in many types of tumors, and downreglation of its expression was associated with the progression of tumor malignancy [99]. Recent studies have shown that let-7 suppresses self-renewal in both normal cells and BCSCs. Let-7 also regulates BCSC phenotypes such as chemoresistance and asymmetric cell division [61]. Several oncogenes, including c-Myc, Ras, HMGA2, cyclin D, and IL-6, have been reported as the targets of let-7 [61,63,99]. HMGA2 and Ras are highly expressed in BCSCs and remarkably repressed in non-BCSCs [61]. A comprehensive pathway involved in let-7 and lin-28 promotes the tumor metastasis and BCSC-induced inflammatory response [63]. Lin-28 is a highly specific embryonic stem cell marker and behaves as a negative regulator of let-7. Let-7 also directly represses lin-28 expression in ES and cancer cells [100].

Bottom Line: CSCs share a variety of biological properties with normal somatic stem cells in self-renewal, the propagation of differentiated progeny, the expression of specific cell markers and stem cell genes, and the utilization of common signaling pathways and the stem cell niche.However, CSCs differ from normal stem cells in their chemoresistance and their tumorigenic and metastatic activities.In addition, we especially focus on the CSCs of breast cancer since the use of neoadjuvant chemotherapy can lead to the enrichment of CSCs in patients with that disease.

View Article: PubMed Central - PubMed

Affiliation: Division of Molecular and Cellular Medicine, National Cancer Center Research Institute, 1-1, Tsukiji 5-chome, Chuo-ku, Tokyo 104-0045, Japan. tochiya@ncc.go.jp.

ABSTRACT
The cancer stem cell (CSC) theory is generally acknowledged as an important field of cancer research, not only as an academic matter but also as a crucial aspect of clinical practice. CSCs share a variety of biological properties with normal somatic stem cells in self-renewal, the propagation of differentiated progeny, the expression of specific cell markers and stem cell genes, and the utilization of common signaling pathways and the stem cell niche. However, CSCs differ from normal stem cells in their chemoresistance and their tumorigenic and metastatic activities. In this review, we focus on recent reports regarding the identification of CSC markers and the molecular mechanism of CSC phenotypes to understand the basic properties and molecular target of CSCs. In addition, we especially focus on the CSCs of breast cancer since the use of neoadjuvant chemotherapy can lead to the enrichment of CSCs in patients with that disease. The identification of CSC markers and an improved understanding of the molecular mechanism of CSC phenotypes should lead to progress in cancer therapy and improved prognoses for patients with cancer.

No MeSH data available.


Related in: MedlinePlus