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How can trillions of cells all with the same genetic information coordinate to form a complex organism? To address this question, Bissell uses the mammary gland as an experimental "organism".

In early work, she found that cells isolated from mammary tissue and cultured on plastic rapidly lost all structural organization while those cultured in the presence of extracellular matrix molecules maintained their complex 3-dimensional structure; evidence for the importance of ECM in maintaining normal tissue structure. Bissell proceeded to demonstrate that ECM components are key in determining the development of a normal or malignant phenotype irrespective of genotype.

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