Not only Cancer Genomes: Part 3
 

The AIRC Plenary Lecture on “the microenvironment and the genome in breast cancer: how tissue architecture informs” was given by an outstanding (despite jet-lag) keynote speaker on the closing day of the 21^st EACR 21 meeting, namely Mina Bissell.

For those of you that are not familiar with the name, Mina Bissell is a Theran-born American biologist and a world-recognized leader in the extracellular matrix (ECM) and microenvironment in regulation of tissue-specific function, with a special emphasis on breast cancer.

In the '80s and '90s Bissell started making her -at that time revolutionary- claims about a holistic approach to cancer. Her claims about the importance of the cell's microenvironment and tissue architecture in the formation of tumours were snubbed at a time in which scientists were busy looking at single point mutations and other discrete genetic modifications in tumours, with the hope that a handful of “bad genes” (ie, oncogenes) would prove to be responsible for cancer. But, alas, simple solutions rarely work for complex problems, and this was also the case of oncogenes as the only cause of cancer.

Mina Bissell's laboratory at Berkeley [1] focuses on how the study of tissue architecture informs breast cancer and in the last three decades her group has developed tridimensional organotypic models to support the hypothesis  of ‘dynamic reciprocity’ first proposed by Bissell in 1982 [2]. According to this hypothesis, the ECM exerts physical and biochemical influences on a cell, which are then transduced by cell surface receptors through the cell’s skeleton and ultimately effects changes in gene expression. In turn the cell, in this now altered state, can remodel the ECM, for instance by inducing expression of matrix metalloproteinases. This feedback mechanism affects not only the cell nucleus, but can also affect other nearby and not so nearby cells [3].

Bissell's work has become a hot topic only in the past few years. In 2003 the journal Nature championed Bissell as the pioneer of the 3-D matrix as ‘biology's new dimension” [4], and more recently the New York Times devoted to her an article titled “Old Ideas Spur New Approaches in Cancer Fight” [5].  Funds have also started to pour in this direction, since  2006 when the National Cancer Institute set up a tumour microenvironment initative, funding ten projects intended to promote and facilitate interdisciplinary collaborations and progress in understanding the role of host stroma in tumorigenesis (TMEN).[6]

In the last few years Bissell has also been frequently invited as a keynote speaker at international conferences, such as EACR 21. This late fame, though, does not seem to have change her nonconformist attitude, and in Oslo she encouraged young researchers and “old passionate ones” to keep on thinking outside the box, referring to a cartoon by the New Yorker [7].


Bissell indicated we should stop reasoning only in terms of cancer genomes and epigenomes -also a big theme at EACR 21 - as a possible way out of the predefined limits to our thinking which our fellow scientists or scientific community impose. As Bissell put it: “We keep on sequencing like there is no tomorrow”, but do not consider that such an approach leaves unanswered a lot of important questions about cancer and, most importantly, feasible and effective ways to treat it.

Another approach to lateral thinking would be not to follow too pedantically keynote speakers' suggestions, as Mina Bissell self-ironically concluded her talk. “As I once was the cat [in the New Yorker cartoon] I've now become the old man, so don't listen to me and follow your intuition”.










References:

[1] Mina Bissell laboratory, website available at: http://www.lbl.gov/LBL-Programs/lifesciences/BissellLab/main.html  (accessed July 5, 2010).

[2] Bissell MJ, Hall HG, Parry G.J How does the extracellular matrix direct gene expression?  Theor Biol 1982;99(1):31-68.

[3] Rønnov-Jessen L, Bissell MJ. Breast cancer by proxy: can the microenvironment be both the cause and consequence? Trends Mol Med 2009; 15(1):5–13.

[4] Abbott A, Cell culture: Biology's new dimension. Nature 2003; 424, 870-872.

[5] Kolata G, Old Ideas Spur New Approaches in Cancer Fight, New York Times December 28, 2009, article available at  http://www.nytimes.com/2009/12/29/health/research/29cancer.html?_r=1&pagewanted=2 (accessed July 5, 2010).

[6] National Cancer Institute “Tumor Microenvironment Initiative”, website available at http://tmen.nci.nih.gov/ (accessed July 5, 2010).

[7] New Yorker Cartoon, Never Think Outside Box, available at: http://www.newyorkerstore.com/Cats/Never-ever-think-outside-the-box/invt/117887(accessed July 5, 2010).



Above Image  Copyright  New Yorker