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Model Systems in Cancer Research: Human cells

Course describing model organisms and examples of their use in cancer research

Acinar Organization in 3D culture

Overexpression of transcription factor C/EBPbeta-2 disrupts normal acinar architecture of human breast epithelial cells, inducing complex multiacinar structures with filled lumens. Molecular Cancer 2005, 4:43

stained acini

Click here 3D movies or on image above to see a webpage containing several movies with optical sections of acini formed in 3D culture. Compare image seen in 'Additional file 2' = Normal to 'Additional file 4'=Aberrant.

Real time imaging of cell motility in 3D culture

Extracellular signal–regulated kinases may promote noninvasive motility in preinvasive mammary tumors. The Journal of Cell Biology, Vol. 179, No. 7, 1555-1567.

motility mammary acini

Click here Real time imaging of acini or on the image above to see a webpage containing several videos comparing motility of cells in mammary acini formed in 3D culture. Compare videos of control acini (video 1, 5) to videos of Raf-ER induced acini (videos 2,3 and 6).

Online resources

Three-dimensional culture is rapidly developing but still not as common as other model systems. We do not have any books dedicated to three-dimensional culture systems in the Arnold library, but I hope the reviews in the class reading materials and the methods papers and protocols on lab websites listed below can guide you to further information. 

Papers about methods used in 3D culture:

1. "Three-dimensional culture models of normal and malignant breast epithelial cells" by Genee Y Lee et al. 

2. "Morphogenesis and oncogenesis of MCF-10A mammary epithelial acini grown in three-dimensional basement membrane cultures" by Jayanta Debnath, Senthil K. Muthuswamy, and Joan S. Brugge.

 

Websites with 3D culture and associated technique protocols:

1. Bissell lab protocols 

2. Brugge lab protocols

3. Muthuswamy lab protocols

Lecture Slides and Papers

Three-dimensional culture of human cells 

Lecture videos are available for viewing in the left column. They will be used during class to illustrate points about modeling cancer progression in 3D culture systems.

Required/Encouraged Reading

1. Great review of the various types of 3D culture. Pros and cons and applications of this model system.

 "Modeling tissue morphogenesis and cancer in 3D" by Yamada KM, Cukierman E.

2. Comprehensive review of the important features of epithelial structures grown in 3D basement membrane cultures, and how such models have been used to investigate the mechanisms associated with tumour initiation and progression.

 "Modelling glandular epithelial cancers in three-dimensional cultures" by Jayanta Debnath & Joan S. Brugge.

3. An excellent short essay that gives an overview of the various 3D culture systems. Covers lessons that are guiding the development of these 3D models, and technical challenges and improvements with an emphasis on imaging.

"The third dimension bridges the gap between cell culture and live tissue" by Francesco Pampaloni, Emmanuel G. Reynaud & Ernst H. K. Stelzer.

4. Short interesting review on the effect of the microenvironment on normal and malignant cells. Includes a good historical perspective and though it is a bit old it also covers tumor stem cells, which is a concept that will be useful for our next lecture.

"Context,tissue plasticity,and cancer:Are tumor stem cells also regulated by the microenvironment?" by Mina J. Bissell and Mark A. LaBarge.

 Additional Reading

1. Article describing a new biomimetic model that may provide a broadly applicable 3D culture system to study the effect of microenvironmental conditions on tumor malignancy in vitro and in vivo.

“Engineering tumors with 3D scaffolds” by Fischbach C et al.

2. Review describing the critical roles that microenvironmental context and tissue architecture play in directing breast development and differentiation an in determining the response to oncogenic insults.

“Of extracellular matrix, scaffolds, and signaling: tissue architecture regulates development, homeostasis, and cancer.” by Nelson CM, Bissell MJ.

On campus resources - FHCRC 3D culture labs

FHCRC scientists using three-dimensional culture models:

1.Beatrice Knudsen: 3D culture of normal and malignant prostate cells.

2. Jim Roberts: 3D culture of primary and immortalized human mammary epithelial cells.

 

Tumor Microenvironment (TMEN) monthly discussion meetings take place on campus. They are from 5-6pm on Thursdays in the Arnold building M1-A305/307. Organized by the PPCR/SPORE, contact Margery Kiso for more information.