Modeling dynamic reciprocity: Engineering three-dimensional culture models of breast architecture, function, and neoplastic transformation

Nelson, Celeste M.; Bissell, Mina J.

doi:10.1016/j.semcancer.2005.05.001

Cited by 301 publications

(248 citation statements)

References 128 publications

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“…Tumorigenic two-dimensional cultures of mammary carcinoma cells could lose their tumorigenicity, at least temporarily, after they had been built into a threedimensional acinar structure in vitro (44). Similar experiments have been performed on liver/hepatocarcinoma systems.…”

Section: Intercellular Surveillance (Microenvironmental Control)mentioning

confidence: 84%

Toward a genetics of cancer resistance

Klein

2009

Proc. Natl. Acad. Sci. U.S.A.

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Two of three humans never get cancer. Even the majority of heavy smokers remain cancer free. Is this a matter of chance, or are there cancer-resistant genotypes? Based on the evidence discussed, it would appear that evolution has favored a limited number of relatively common resistance genes that may nip incipient cancerous foci in the bud, i.e., to stop them at their inception. It is further suggested that resistance genes may act at the level of tissue organization in a dominant fashion.

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Section: Intercellular Surveillance (Microenvironmental Control)mentioning

confidence: 84%

Toward a genetics of cancer resistance

Klein

2009

Proc. Natl. Acad. Sci. U.S.A.

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“…Role of the antiapoptotic factor G1P3 in breast cancer V Cheriyath et al 2001; Debnath et al, 2003;Nelson and Bissell, 2005). This suggested that G1P3 overexpression may lead to preneoplastic lesions in breast epithelium.…”

Section: Discussionmentioning

confidence: 99%

G1P3, an interferon- and estrogen-induced survival protein contributes to hyperplasia, tamoxifen resistance and poor outcomes in breast cancer

et al. 2011

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Hormonally regulated survival factors can have an important role in breast cancer. Here we elucidate G1P3, a survival protein induced by interferons (IFNs), as a target of estrogen signaling and a contributor to poor outcomes in estrogen receptor-positive (ER þ ) breast cancer. Compared with normal breast tissue, G1P3 was upregulated in the malignant epithelium (50 Â higher) and was induced by estrogen ex vivo. In accord with its overexpression in early stages of breast cancer (hyperplasia and ductal carcinoma in situ), in morphogenesis assays G1P3 enhanced the survival of MCF10A acinar luminal cells causing hyperplasia by suppressing detachmentinduced loss of mitochondrial potential and apoptosis (anoikis). In cells undergoing anoikis, G1P3 attenuated the induction of Bim protein, a proapoptotic member of the Bcl-2 family and reversed the downmodulation of Bcl-2 protein. Downregulation of G1P3 induced spontaneous apoptosis in BT-549 breast cancer cells and significantly reduced the growth of ER þ breast cancer cell MCF7 (Pp0.01), further suggesting its prosurvival activity. In agreement with its induction by estrogen, G1P3 antagonized tamoxifen, an inhibitor of ER in MCF7 cells. More importantly, elevated expression of G1P3 was significantly associated with decreased relapsefree and overall survival in ER þ breast cancer patients (Pp0.01). Our studies suggest that elevated expression of G1P3 may perturb canonical tumor-suppressing activity of IFNs partly by affecting the balance of pro-and antiapoptotic members of Bcl-2 family proteins, leading to breast cancer development and resistance to therapies.

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“…52 For genuine 3D cell culture, hydrogel models have been typically built with hydrated collagen, which is a major protein component of connective tissues. 34 Such models have been increasingly adopted in 3D cell culture systems and cell migration assays, 17,33,50 as these 3D collagen matrix models provide a more physiologically relevant and controlled environments for migrating cells, 53 and also allow for cell-induced remodeling to the matrix through extracellular matrix (ECM) protein synthesis, proteolytic degradation and matrix contraction.…”

Section: Introductionmentioning

confidence: 99%

Effects of Migrating Cell-Induced Matrix Reorganization on 3D Cancer Cell Migration

et al. 2014

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Abstract-The migration of cells is fundamental to a number of physiological/pathological processes, ranging from embryonic development, tissue regeneration to cancer metastasis. Current research on cell migration is largely based on simplified in vitro models that assume a homogeneous microenvironment and overlook the modification of extracellular matrix (ECM) by the cells. To address this shortcoming, we developed a nested threedimensional (3D) collagen hydrogel model mimicking the connective tissue confronted by highly malignant breast cancer cells, MDA-MB-231. Strikingly, our findings revealed two distinct cell migration patterns: a rapid and directionally persistent collective migration of the leader cells and a more randomized migration in the regions that have previously been significantly modified by cells. The cell-induced modifications, which typically include clustering and alignment of fibers, effectively segmented the matrix into smaller sub-regions. Our results suggest that in an elastic 3D matrix, the presence of adjacent cells that have modified the matrix may in fact become physical hurdle to a migrating cell. Furthermore, our study emphasizes the need for a micromechanical understanding in the context of cancer invasion that allows for cell-induced modification of ECM and a heterogeneous cell migration.

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Modeling dynamic reciprocity: Engineering three-dimensional culture models of breast architecture, function, and neoplastic transformation

Cited by 301 publications

References 128 publications

Toward a genetics of cancer resistance

Toward a genetics of cancer resistance

G1P3, an interferon- and estrogen-induced survival protein contributes to hyperplasia, tamoxifen resistance and poor outcomes in breast cancer

Effects of Migrating Cell-Induced Matrix Reorganization on 3D Cancer Cell Migration

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