来源生物谷

2007-8-14 22:36:56

Science：肿瘤生长无需少数肿瘤干细胞的驱动

生物谷

生物谷报道：肿瘤干细胞假说认为肿瘤生长是由肿瘤细胞的少数亚细胞群驱动的。支持这一让人充满兴趣的观点的大多数证据来自异种移植实验，在这些实验中，人类白血病细胞被移植到免疫缺损小鼠中生长。发表在七月二十日的《科学》杂志上的一篇报道结果显示，将小鼠来源的淋巴瘤和白血病移植到组织相容的小鼠身上，很高频率（至少十分之一）的肿瘤细胞可以种植出新生肿瘤。

研究人员认为，在异种移植实验中肿瘤维持细胞发生频率低，反映了人类肿瘤细胞适应外界（小鼠）环境生长的能力有限。

原文出处：

Science 20 July 2007 Vol 317, Issue 5836

Tumor Growth Need Not Be Driven by Rare Cancer Stem Cells

Priscilla N. Kelly, Aleksandar Dakic, Jerry M. Adams, Stephen L. Nutt, and Andreas Strasser
Science 20 July 2007: 337.
Many of the lymphoma and leukemia cells in mice can seed new tumors, a result inconsistent with the hypothesis that tumor growth is driven by rare cancer stem cells.
Abstract »| Full Text »| PDF »| Supporting Online Material »|

作者简介：

Dr. Andreas Strasser

Molecular Genetics of Cancer Division

Research Overview:

Dr Strasser and his team are investigating the control of apoptosis, the cell death program essential for development and homeostasis. By using transgenic mice over-expressing the cell death inhibitor bcl-2 and knock-out mice lacking one of its antagonists, they demonstrated that abnormalities in the control of apoptosis can cause autoimmune disease or cancer and render tumour cells refractory to anti-cancer therapy. Dr Strasser and his co-workers established that mammalian cells have two distinct signalling pathways leading to apoptosis, one triggered by ligation of cell surface "death receptors" and the other by certain developmental cues, cytokine deprivation or stress signals. Using genetically modified mice they could determine signalling mechanisms that are responsible for killing useless or potentially dangerous at the different checkpoints during lymphocyte development. Using biochemical and molecular biology techniques, Dr Strasser and his team discovered novel regulators that are essential for initiation of programmed cell death and showed that they function as sentinels for damage to various vital intra-cellular structures, such as the cytoskeleton. These discoveries have major implications for cancer research, developmental biology and immunology and suggest novel therapeutic strategies for tumours, autoimmunity and degenerative diseases.
Current research interests include identification of the signalling pathways that mediate developmentally programmed cell death in mammals and those that are responsible for chemotherapy-induced killing of cancer cells, with the goal to develop improved strategies for treatment of cancer and autoimmune diseases.

Major Publications

1. Strasser A, Harris AW, Bath ML, Cory S.

Novel primitive lymphoid tumours induced in transgenic mice by cooperation

between myc and bcl-2. Nature. 1990 Nov 22;348(6299):331-3.

PMID: 2250704 [PubMed - indexed for MEDLINE]

2. Strasser A, Whittingham S, Vaux DL, Bath ML, Adams JM, Cory S, Harris AW.

Enforced BCL2 expression in B-lymphoid cells prolongs antibody responses and

elicits autoimmune disease. Proc Natl Acad Sci U S A. 1991 Oct 1;88(19):8661-5.

PMID: 1924327 [PubMed - indexed for MEDLINE]

3. Strasser A, Harris AW, Cory S.

bcl-2 transgene inhibits T cell death and perturbs thymic self-censorship. Cell. 1991 Nov 29;67(5):889-99.

PMID: 1959134 [PubMed - indexed for MEDLINE]

4. Strasser A, Harris AW, Corcoran LM, Cory S.

bcl-2 expression promotes B- but not T-lymphoid development in scid mice. Nature. 1994 Mar 31;368(6470):457-60.

PMID: 8133891 [PubMed - indexed for MEDLINE]

5. Strasser A, Harris AW, Jacks T, Cory S.

DNA damage can induce apoptosis in proliferating lymphoid cells via

p53-independent mechanisms inhibitable by bcl-2. Cell. 1994 Oct 21;79(2):329-39.

PMID: 7954799 [PubMed - indexed for MEDLINE]

6. Strasser A, Harris AW, Huang DC, Krammer PH, Cory S.

bcl-2 and Fas/APO-1 regulate distinct pathways to lymphocyte apoptosis. EMBO J. 1995 Dec 15;14(24):6136-47.

PMID: 8557033 [PubMed - indexed for MEDLINE]

7. Maraskovsky E, O'Reilly LA, Teepe M, Corcoran LM, Peschon JJ, Strasser A.

bcl-2 can rescue T lymphocyte development in interleukin-7 receptor-deficient

mice but not in mutant rag-1-/- mice. Cell. 1997 Jun 27;89(7):1011-9.

PMID: 9215624 [PubMed - indexed for MEDLINE]

8. Newton K, Harris AW, Bath ML, Smith KG, Strasser A.

A dominant interfering mutant of FADD/MORT1 enhances deletion of autoreactive

thymocytes and inhibits proliferation of mature T lymphocytes. EMBO J. 1998 Feb 2;17(3):706-18.

PMID: 9450996 [PubMed - indexed for MEDLINE]

9. Puthalakath H, Huang DC, O'Reilly LA, King SM, Strasser A.

The proapoptotic activity of the bcl-2 family member Bim is regulated by

interaction with the dynein motor complex. Mol Cell. 1999 Mar;3(3):287-96.

PMID: 10198631 [PubMed - indexed for MEDLINE]

10. Bouillet P, Metcalf D, Huang DC, Tarlinton DM, Kay TW, Kontgen F, Adams JM, Strasser A.

Proapoptotic bcl-2 relative Bim required for certain apoptotic responses,

leukocyte homeostasis, and to preclude autoimmunity. Science. 1999 Nov 26;286(5445):1735-8.

PMID: 10576740 [PubMed - indexed for MEDLINE]

11. Puthalakath H, Villunger A, O'Reilly LA, Beaumont JG, Coultas L, Cheney RE, Huang DC, Strasser A.

Bmf: a proapoptotic BH3-only protein regulated by interaction with the myosin V

actin motor complex, activated by anoikis. Science. 2001 Sep 7;293(5536):1829-32. Erratum in: Science 2002 Aug 16;297(5584):1122.

PMID: 11546872 [PubMed - indexed for MEDLINE]

12. Bouillet P, Purton JF, Godfrey DI, Zhang LC, Coultas L, Puthalakath H, Pellegrini M, Cory S, Adams JM, Strasser A.

BH3-only bcl-2 family member Bim is required for apoptosis of autoreactive

thymocytes. Nature. 2002 Feb 21;415(6874):922-6. Erratum in: Nature 2002 Jul 4;618(6893):108.

PMID: 11859372 [PubMed - indexed for MEDLINE]

13. Marsden VS, O'Connor L, O'Reilly LA, Silke J, Metcalf D, Ekert PG, Huang DC, Cecconi F, Kuida K, Tomaselli KJ, Roy S, Nicholson DW, Vaux DL, Bouillet P, Adams JM, Strasser A.

Apoptosis initiated by bcl-2-regulated caspase activation independently of the

cytochrome c/Apaf-1/caspase-9 apoptosome. Nature. 2002 Oct 10;419(6907):634-7. Epub 2002 Sep 25.

PMID: 12374983 [PubMed - indexed for MEDLINE]

14. Villunger A, Michalak EM, Coultas L, Mullauer F, Bock G, Ausserlechner MJ, Adams JM, Strasser A.

p53- and drug-induced apoptotic responses mediated by BH3-only proteins puma

and noxa. Science. 2003 Nov 7;302(5647):1036-8. Epub 2003 Sep 18.

PMID: 14500851 [PubMed - indexed for MEDLINE]

15. Strasser A, O'Connor L, Dixit VM.

Apoptosis signaling. Annu Rev Biochem. 2000;69:217-45. Review.

PMID: 10966458 [PubMed - indexed for MEDLINE]

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