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. Author manuscript; available in PMC: 2015 Jan 1.
Published in final edited form as: Wiley Interdiscip Rev Membr Transp Signal. 2013 Nov 18;3(2):147–163. doi: 10.1002/wdev.130

Figure 2. Organ specificity in 3D: an emergent property of a multicomponent interaction network.

Figure 2

Systems biology potentially reveals the relationship between homeostasis and cancer. Shown here is an n-dimensional interaction space with the axes representing protein expression levels.

State I depicts the phenotypic organization of normal/non-malignant mammary gland as an acinus that emerges if the mammary epithelial cells are placed in lrECM. The acinus is characterized by cellular quiescence, basal and apical polarity and lumen formation. An intact laminin-111-rich BM ensures repression of oncogenic signaling pathways and downregulation of a metalloproteinase MMP979, 101, 104.

State II depicts an amorphous phenotype with loss in acinar organization and polarity and cell proliferation, all of which occur when proteolytic MMPs are overexpressed in either non-malignant human breast cells (MMP9)104 or in mammary glands in vivo (MMP3)130. Overexpression of MMP results in proteolysis and destruction of the BM, leading to loss in tissue specificity and eventually tumors131.

State III depicts a reverted and re-organized mammary epithelial phenotype with growth arrest, a partial restoration of polarity (only basal polarity returns). The reversion occurs when one or more of the oncogenic signaling pathways or MMPs are inhibited99, 101.