Breast Cancer in 3D Culture

 I came across this research article in Journal of Cancer and I found this research very interesting moreover, it is new research for breast cancer. The title of the article is “Optimizing 3D Culture System to Study the Interaction between Epithelial Breast Cancer and Its Surrounding Fibroblasts,” and it was done by Liyuan Li, and Yi Lu from department of Pathology and Laboratory Medicine, University of Tennessee Health Science Center, Memphis, Tennessee. Breast cancer (BCa) is the most commonly diagnosed cancer and the second leading cause of cancer deaths in American women today. It is estimated that there were 207,090 new cases of BCa and 39,840 BCa deaths in American women in 2010. The estimation of newly developed anti-cancer drugs are usually performed initially in the traditional two-dimensional (2D) culture; however, most drugs that show promise in the 2D culture are rarely effective in vivo in animals or clinical trials, partially because the clinically relevant breast tumors do not exist as a monolayer, stand-alone entity in vivo. Thus, to better study BCa malignant progression that involves interplay between different cell types and to accurately evaluate the therapeutic efficacy of anticancer drugs, a better in vitro co-culture model that more closely resembles the in vivo BCa growth environment should be identified and used.

 The research is different from previous ones because it gives a new view of breast cancer with 3D culture. To explains what is the gene that causes breast cancer is hard, but this is a short summery of the mains reason for this research. The researchers said that Stromal fibroblasts are suggested to be a key determinant in the malignant progression of breast cancer. To find an in vitro culture model that best mimics the in vivo tumor microenvironment so we can study the effects of stromal fibroblasts on breast cancer progression; we evaluated several three-dimensional (3D) co-culture models in order to identify the most suitable culture model for our study. The purpose of our study is to co-culturing malignant mouse breast cancer 4T1 cells and murine embryonic fibroblasts (MEF) to form spheroids with matrigel. We found the best culture model for forming the 4T1 aggregates/spheroids was, in the absence of fibroblast, by growing 4T1 cells in the culture wells precoated with matrigel and in the overlay medium containing 2% matrigel. We chose this model as our standard 3D culture to co-culture 4T1 and MEF cells at different ratios. We found that the amount of MEF in the 4T1/MEF mixture affects the morphology of 4T1/MEF aggregates/spheroids: the higher the ratio of MEF in the mixture, the more ductal structures formed among the aggregates, and the more polarized-like alveolar structures they tended to become. Fibroblasts produced protection for the breast cancer cells in the 3D culture, as aggregates/spheroids formed by breast-cancer cells alone were more sensitive to cytotoxic chemo-agents than aggregates formed by the breast-cancer/fibroblast mixture.

They used mouse mammary carcinoma cell line 4T1 was grown containing 10% fetal brovine serum. Then murine embryonic fibroblasts (MEF) were grown in dulbecco’s modified Eagle medium with use of high glucose. All cells were grown in medium contain 100units/ml penicillin and 100ug/ml streptomycin and they were incubated at 37C in 5% CO2.  There are a lot more steps , but I am including the link for the article so anyone want to read all details can get do it. Various 3D culture models were examined to determine the suitable BCa culture system for our study: (i) BCa cells growing in culture wells precoated with matrigel (BD Biosciences, Bedford, MA) and in regular medium (3D-base), (ii) BCa cells growing in culture wells without base matrigel and in medium containing 2% matrigel (3D-no base and embedded), or (iii) BCa cells growing in culture wells precoated with matrigel and in medium containing 2% matrigel (3D-base and embedded). The last system (3D-base and embedded) was chosen in our studies and is herein referred as the “standard 3D culture” system throughout.

 

The findings of the research was that the 3D culture has been increasingly accepted as a more physiologically relevant and predictive model. The tumor growth is not only determined by malignant cancer cells, but also by the tumor microenvironments. The co-culture 3D system should provide a better in vitro culture model for studying tumor progression that involves interplay between different cell types and evaluation of efficacy of anticancer drugs. For example, our results showed YC-1, an anti-cancer chemo-agent that induces cell cycle arrest and apoptosis via HIF-1α suppression, killed BCa cells much less effectively in the 3D culture than in the 2D culture, consistent with the fact that many drugs developed based on the 2D culture do not work effectively in the clinical situation. These results suggest that in vitro drug evaluation in 3D culture may provide a better clinical relevant prediction than the traditional 2D culture. The fact that the complete/polarized alveolar/ductal mammary gland structure was not formed in our 3D co-culture may be consistent to the previous observation that the pathogenesis of epithelial tumor required the disruption of the intact polarized structure and with further modifications, the usage of such a 3D co-culture model can be widely applied in studying the interaction and interplay between breast tumor cells and stroma fibroblasts.

            This research like all other researches that have been done for breast cancer is a milestone to find a better way to cure the cause of the tumor insisted of just curing the symptoms. The research also talks about the drugs that can be used in 3D culture more effectively. We all can hope that one day we find a way that we can cure each patient of breast cancer or any cancer because it is a horrible disease that decreases patient’s life from years to months and days.  

 

 

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http://www.jcancer.org/v02p0458.htm

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4 Comments

  1. iamdanielhuang said,

    September 18, 2011 at 11:30 pm

    It is scary that breast cancer contribute to such a large death toll. Breast cancer is also possible for me correct? Is it because of the smaller number of cases that we rarely hear about it? Also is it any more or less dangerous than breast cancer for women?

  2. carlosgreat said,

    September 19, 2011 at 1:54 am

    It is sad to think that we still have not appropriated enough resources and tools in trying to understand and find cure for so many illnesses that inflict our bodies. I do share your enthusiasm that being aware and starting at some point is a good approach than just leaving the responsibilities as well as inflictions to future generations. I wish I had some sort of 3D environment, when I was doing DNA replication on my Biology lab. I would have seen more effective and faster results :). Very informative post. Do provide us with more links within your text … it would be nice to just click on “4T1” and get a definition of it.

  3. lineahann said,

    September 19, 2011 at 5:46 am

    Very interesting post, i agree with carlos that adding definitions would help. i really enjoy reading your posts, i like hearing about the current research on diseases like cancer that effect so many of us. I think it’s horrible that it is nearly impossible for most of us to be able to afford treatment to a disease that is so common. I hope that i will see an affordable cure in my lifetime.

  4. October 14, 2011 at 7:54 pm

    […] on her blog post Breast Cancer in 3D Culture explains the effectiveness on doing breast cancer treatment research entirely in a 3D environment […]


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