Biological and molecular heterogeneity of breast cancers correlates with their cancer stem cell content (Cell, 2010, 140:62-73)

報告日期: 2010/04/16
報告時間: 17:10/18:00
報告學生: 楊明哲(英文報告)
講評老師: 沈孟儒
附件下載:

http://basicmed.med.ncku.edu.tw/admin/up_img/990416-3.pdf

Biological and Molecular Heterogeneity of Breast Cancers Correlates with Their Cancer Stem Cell Content

 

報告學生:楊明哲

講評老師:沈孟儒 教授

時間 : 99.04.16 (17:10~18:00)

地點 : 602 教室

 

Abstract:

Human breast carcinomas have heterogeneous pathologies and molecular profiles. The seemingly simple cytoarchitecture of the mammary gland is difficult to settle the variety of breast cancer phenotypes. Despite it has morphological simplicity, the mammary gland may be functionally complex and molecularly heterogeneous. With this hypothesis, the authors used the normal human mammary stem cells (hNMSCs) signature to question the expression data sets of breast cancers.

This study demonstrated the purification and molecular characterization of hNMSCs from cultured mammospheres. The authors stained human mammosphere cultures with a fluorescent marker PKH26 which labels quiescent cells but not proliferating cells as it will lost by dilution. They reported a method, based on labeling hNMSCs and mammospheres formation that enables to obtain pure population. The authors compared microarray expression profiles of PKH26-positive cells and PKH26-negative cells. A gene signature for hNMSCs has been identified. Some identified markers of the hNMSC signature can be use to isolate SCs from normal gland and breast tumors. Poorly differentiated tumors expressed higher levels of genes in the hNMSCs gene signature compared with well-differentiated tumors. CSCs isolated from poorly differentiated tumors using markers from the hNMSCs signature formed mammospheres in culture and tumor xenografts more efficiently than isolated from well-differentiated tumors.

Because the different number of cancer stem cells (CSCs) present within different types of breast tumors, they found the signature could classify breast cancers according to their biological and molecular features. This study proposed a model of breast tumorigenesis to resolve the incongruence between the complexity of breast cancer phenotypes and the simplicity of the normal breast tissue.  

Summary of this paper : j Human mammary stem cells (hNMSCs) can be isolated to pure population k hNMSCs have a special molecular signature and the signature characterizes breast cancers of different grades and molecular subtypes l The content of breast cancer stem cell is related to tumor differentiation level and prognosis.

 

References:

1.   Salvatore Pece, Daniela Tosoni, Stefano Confalonieri, Giovanni Mazzarol, Manuela Vecchi, Simona Ronzoni, Loris Bernard, Giuseppe Viale, Pier Giuseppe Pelicci, and Pier Paolo Di Fiore Biological and Molecular Heterogeneity of Breast Cancers Correlates with Their Cancer Stem Cell Content. Cell. 140, 62-73. 2010. (this issue)

2.    John Stingl and Carlos Caldas. Molecular heterogeneity of breast carcinomas and the cancer stem cell hypothesis. Nature. 7, 791-799. 2007.

3.   Angelo Cicalese, Giuseppina Bonizzi, Cristina E. Pasi, Mario Faretta, Simona Ronzoni, Barbara Giulini, Cathrin Brisken, Saverio Minucci, Pier Paolo Di Fiore, and Pier Giuseppe Pelicci. The Tumor Suppressor p53 Regulates Polarity of Self-Renewing Divisions in Mammary Stem Cells. Cell. 138, 1083-1095. 2009.