Gain in cellular organization of inflammatory breast cancer: A 3D in vitro model that mimics the in vivo metastasis.

Department of Biology, City University of New York, The City College of New York 138th and Convent Avenue, New York, NY 10031, USA.
BMC Cancer (Impact Factor: 3.32). 12/2009; 9:462. DOI: 10.1186/1471-2407-9-462
Source: PubMed

ABSTRACT The initial step of metastasis in carcinomas, often referred to as the epithelial-mesenchymal transition (EMT), occurs via the loss of adherens junctions (e.g. cadherins) by the tumor embolus. This leads to a subsequent loss of cell polarity and cellular differentiation and organization, enabling cells of the embolus to become motile and invasive. However highly malignant inflammatory breast cancer (IBC) over-expresses E-cadherin. The human xenograft model of IBC (MARY-X), like IBC, displays the signature phenotype of an exaggerated degree of lymphovascular invasion (LVI) in situ by tumor emboli. An intact E-cadherin/alpha, beta-catenin axis mediates the tight, compact clump of cells found both in vitro and in vivo as spheroids and tumor emboli, respectively.
Using electron microscopy and focused ion beam milling to acquire in situ sections, we performed ultrastructural analysis of both an IBC and non-IBC, E-cadherin positive cell line to determine if retention of this adhesion molecule contributed to cellular organization.
Here we report through ultrastructural analysis that IBC exhibits a high degree of cellular organization with polar elements such as apical/lateral positioning of E-cadherin, apical surface microvilli, and tortuous lumen-like (canalis) structures. In contrast, agarose-induced spheroids of MCF-7, a weakly invasive E-cadherin positive breast carcinoma cell line, do not exhibit ultrastructural polar features.
This study has determined that the highly metastatic IBC with an exaggerated malignant phenotype challenges conventional wisdom in that instead of displaying a loss of cellular organization, IBC acquires a highly structured architecture.These findings suggest that the metastatic efficiency might be linked to the formation and maintenance of these architectural features. The comparative architectural features of both the spheroid and embolus of MARY-X provide an in vitro model with tractable in vivo applications.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Inflammatory breast cancer (IBC) is a highly metastatic and fatal form of breast cancer. In fact, IBC is characterized by specific morphological, phenotypic, and biological properties that distinguish it from non-IBC. The aggressive behavior of IBC being more common among young women and the low survival rate alarmed researchers to explore the disease biology. Despite the basic and translational studies needed to understand IBC disease biology and identify specific biomarkers, studies are limited by few available IBC cell lines, experimental models, and paucity of patient samples. Above all, in the last decade, researchers were able to identify new factors that may play a crucial role in IBC progression. Among identified factors are cytokines, chemokines, growth factors, and proteases. In addition, viral infection was also suggested to participate in the etiology of IBC disease. In this review, we present novel factors suggested by different studies to contribute to the etiology of IBC and the proposed new therapeutic insights.
    Journal of Advanced Research 06/2013; 5(5). DOI:10.1016/j.jare.2013.06.004
  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: Cell culture is characterized by maintaining live cells in the laboratory regardless of the organism in which they originated. This technique has contributed to better understanding of molecular cell mechanisms, permitting important scientific advances, for example, concerning vaccine production and tumor cell biology. Three-dimensional (3D) cell culture initially derived from commonly used cell cultures (monolayer cell cultures). As a particularity, a 3D cell culture permits cells to explore the three dimensions of the space thereby increasing cell-cell interactions, as well as interaction with the environment. When grown in this system, cells form structures known as multicelullar spheroids. The interior of these spheroids present cell heterogeneity, microenvironment formation and different exposure to factors, such as nutrients and oxygen. Owing to the fact that these characteristics are very similar to those of in vivo avascular tumors, 3D cell culture advanced in various research lines, thus becoming a widely used model in radiology and chemotherapy essays. In studies related to breast cancer biology, spheroids are becoming widely used in the aim to comprehend luminal space morphogenesis.
  • [Show abstract] [Hide abstract]
    ABSTRACT: The recreation of an in vitro microenvironment to understand and manipulate the proliferation and migration of invasive breast cancer cells may allow one to put a halt to their metastasis capacity. Invasive cancer cells have been linked to embryonic stem (ES) cells as they possess certain similar characteristics and gene signatures. Embryonic microenvironments have the potential to reprogram cancer cells into a less invasive phenotype and help elucidate tumorigenesis and metastasis. In this study, we explored the feasibility of reconstructing embryonic microenvironments using mouse ES cells cultured in alginate hydrogel and investigated the interactions of ES cells and highly invasive breast cancer cells in 2D, 2&1/2D, and 3D cultures. Results showed that mouse ES cells inhibited the growth and tumor spheroid formation of breast cancer cells. The mouse ES cell microenvironment was further constructed and optimized in 3D alginate hydrogel microbeads, and co-cultured with breast cancer cells. Migration analysis displayed a significant reduction in the average velocity and trajectory of breast cancer cell locomotion compared to control, suggesting that bioengineered mouse ES cell microenvironments inhibited the proliferation and migration of breast cancer cells. This study may act as a platform to open up new options to understand and harness tumor cell plasticity and develop therapeutics for metastatic breast cancer.
    Biomaterials 03/2011; 32(17):4130-9. DOI:10.1016/j.biomaterials.2011.02.035 · 8.31 Impact Factor

Preview (2 Sources)

1 Download
Available from