WOW--identification of tumor stem cells in her2+ breast cancer

[Lani]

Cancer Res. 2007 Sep 15;67(18):8671-81.
Identification of Tumorsphere- and Tumor-Initiating Cells in HER2/Neu-Induced Mammary Tumors.

Liu JC, Deng T, Lehal RS, Kim J, Zacksenhaus E.
Division of Cell and Molecular Biology, Toronto General Research Institute-University Health Network; and Departments of Medical Biophysics, Laboratory Medicine and Pathobiology, and Medicine, University of Toronto, Toronto, Ontario, Canada.
A variety of human malignancies, including breast cancer, are thought to be organized in a hierarchy, whereby a relatively minor population of tumor initiating cells (TIC) is responsible for tumor growth and the vast majority of remaining cells is nontumorigenic. Analysis of TICs in model systems of breast cancer would offer uniform and accessible source of tumor cells and the power of mouse genetics to dissect these rare cells. The HER2/Neu proto-oncogene is overexpressed in an aggressive form of human breast cancer. Mouse mammary tumor virus (MMTV)-Neu transgenic mice develop mammary tumors that mimic human HER2 subtype breast cancer. Here, we report on the functional identification of mouse HER2/Neu TICs that can induce tumors after transplantation into the mammary gland of recipient mice. Secondary tumors formed after injecting MMTV-Neu TICs resemble primary tumors in the original transgenic mice and are organized in a hierarchy containing TICs as well as their nontumorigenic descendants. To study MMTV-Neu TICs in vitro, we grew tumorspheres under nonadherent culture conditions. Tumorsphere forming units (TFU) capable of producing tumorspheres retained tumorigenic potential and were indistinguishable by several criteria from TICs. Interestingly, MMTV-Neu TICs and TFUs were committed to the luminal cell fate when induced to differentiate in vitro. Our data define reproducible characteristics of the MMTV-Neu TIC and TFU, which help to explain marker expression profiles of HER2-positive breast cancer. In addition, the similarity between TICs and TFUs in this system provides a rationale for TFU-based screens to target tumor-initiating cells in HER2(+) breast cancer. [Cancer Res 2007;67(18):8671-81].
PMID: 17875707 [PubMed - in process]

[chrisy]

WOW is right!

Now let's get crackin on that targeted therapy!

[Hopeful]

Lani,

Thank you for this virtual explosion of information; 5 terrific posts today alone.

Is there any information on how long MMTV takes to induce bc in mice? Is this a virus that can lay dormant for a long time (like Herpes simplex) or is it a more acute infection?

Thanks,

Hopeful

[Lani]

the articles I have read quickly as I am a vegetarian and hate to think about what they are doing to the poor mice. The articles I have read are about MMTV- induced purposely in lab animals--haven't a clue about how it occurs in nature(if anyone does).

Will try to post the "methods" section of an article having to do with when/how they induced the MMTV (they do it in very abnormal lab mice--usually they are immune-deficient, sometimes diabetic, etc) so it is far from "physiologic" or how it might happen in real life.

Even if I provide you with a description pf how they do it and how long it takes to develop the tumors and how long they wait to "sacrifice" the mice , I don't know how you would interpret that with respect to how it might occur in people. Even though what appears to be the human version of the virus shares so many genes (high % homology), even one different version of one gene can change how a tumor behaves.

Hope this helped!