The Differentiated State of Normal and Malignant Cells or How to Define a “Normal” Cell in Culture

Bissell, Mina J.

doi:10.1016/s0074-7696(08)61130-4

Cited by 197 publications

(121 citation statements)

References 318 publications

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“…Alterations in cell morphology and gene expression have been observed in cells cultured in two-dimensional models compared with those grown in vivo. 33,34 This is thought to be due to the absence of tissue-specific architecture as well as loss of signaling from the extracellular matrix. 34,35 As an alternative to two-dimensional culture methods, three-dimensional scaffolds have been developed as culture mediums that, due to their inherent structure, resemble tumor architecture, enabling many interactions in the extracellular matrix that appear to be critical for cell growth to engage.…”

Section: Discussionmentioning

confidence: 99%

Enrichment of breast cancer stem-like cells by growth on electrospun polycaprolactone-chitosan nanofiber scaffolds

Sims‐Mourtada¹,

Niamat²,

Samuel³

et al. 2014

IJN

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A small population of highly tumorigenic breast cancer cells has recently been identified. These cells, known as breast-cancer stem-like cells (BCSC), express markers similar to mammary stem cells, and are highly resistant to chemotherapy. Currently, study of BCSC is hampered by the inability to propagate these cells in tissue culture without inducing differentiation. Recently, it was reported that proliferation and differentiation can be modified by culturing cells on electrospun nanofibers. Here, we sought to characterize the chemoresistance and stem-like properties of breast cancer cell lines grown on nanofiber scaffolds. Cells cultured on three-dimensional templates of electrospun poly( ε -caprolactone)-chitosan nanofibers showed increases in mammary stem cell markers and in sphere-forming ability compared with cells cultured on polystyrene culture dishes. There was no increase in proliferation of stem cell populations, indicating that culture on nanofibers may inhibit differentiation of BCSC. The increase in stemness was accompanied by increases in resistance to docetaxel and doxorubicin. These data indicate that BCSC populations are enriched in cells cultured on electrospun poly( ε -caprolactone)-chitosan nanofibers, scaffolds that may provide a useful system to study BCSC and their response to anticancer drug treatment.

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Section: Discussionmentioning

confidence: 99%

Enrichment of breast cancer stem-like cells by growth on electrospun polycaprolactone-chitosan nanofiber scaffolds

Sims‐Mourtada¹,

Niamat²,

Samuel³

et al. 2014

IJN

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“…Without this molecular segregation and cellular organization, specialized function is often lost. For example, breast epithelia will only produce milk in an environment that supports apical-basal polarization 3 . The establishment and the maintenance of apical-basal cell polarity and eventually the depolarization of a cell is a complex process controlled by a set of core protein complexes.…”

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confidence: 99%

AmotL2 disrupts apical–basal cell polarity and promotes tumour invasion

et al. 2014

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The establishment and maintenance of apical-basal cell polarity is essential for the functionality of glandular epithelia. Cell polarity is often lost in advanced tumours correlating with acquisition of invasive and malignant properties. Despite extensive knowledge regarding the formation and maintenance of polarity, the mechanisms that deregulate polarity in metastasizing cells remain to be fully characterized. Here we show that AmotL2 expression correlates with loss of tissue architecture in tumours from human breast and colon cancer patients. We further show that hypoxic stress results in activation of c-Fos-dependent expression of AmotL2 leading to loss of polarity. c-Fos/hypoxia-induced p60 AmotL2 interacts with the Crb3 and Par3 polarity complexes retaining them in large vesicles and preventing them from reaching the apical membrane. The resulting loss of polarity potentiates the response to invasive cues in vitro and in vivo in mice. These data provide a molecular mechanism how hypoxic stress deregulates cell polarity during tumour progression.

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“…Unfortunately, the expression of differentiated functions is frequently unstable under conditions of continuous cell culture (1)(2)(3)(4)(5)(6)(7). Although overgrowth ofthe differentiated cell type by "fibroblastoid cells" is often invoked as the cause in primary cultures, there is good evidence in some systems that differentiated diploid cells can "dedifferentiate" and reduce their synthesis of differentiated products (2,3,7). This loss of differentiated functions is also observed in cloned established cell lines where, if overgrowth is the cause, it is overgrowth by a dedifferentiated variant arising within the cloned population .…”

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confidence: 99%

Control of differentiation in heterokaryons and hybrids involving differentiation-defective myoblast variants.

Wright¹

1984

The Journal of Cell Biology

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Clones of differentiation-defective myoblasts were isolated by selecting clones of L6 rat myoblasts that did not form myotubes under differentiation-stimulating conditions. Rat skeletal myosin light chain synthesis was induced in heterokaryons formed by fusing these defective myoblasts to differentiated chick skeletal myocytes. This indicates that the structural gene for this muscle protein was still responsive to chick inducing factors and that the defective myoblasts were not producing large quantities of molecules that dominantly suppressed the expression of differentiated functions . The regulation of the decision to differentiate was then examined in hybrids between differentiation-defective myoblasts and differentiation-competent myoblasts . Staining with antimyosin antibodies showed that the defective myoblasts and homotypic hybrids formed by fusing defective myoblasts to themselves could in fact differentiate, but did so more than a thousand times less frequently than the 64% differentiation achieved by competent L6 myoblasts or homotypic competent x competent L6 hybrids . Heterotypic hybrids between differentiation-defective myoblasts and competent L6 cells exhibited an intermediate behavior of -1% differentiation . A theoretical model for the regulation of the commitment to terminal differentiation is proposed that could explain these results by invoking the need to achieve threshold levels of secondary inducing molecules in response to differentiation-stimulating conditions. This model helps explain many of the stochastic aspects of cell differentiation .During the past twenty years cultured cells have become one ofthe most,important tools for the study ofcell differentiation . Unfortunately, the expression of differentiated functions is frequently unstable under conditions of continuous cell culture (1-7). Although overgrowth ofthe differentiated cell type by "fibroblastoid cells" is often invoked as the cause in primary cultures, there is good evidence in some systems that differentiated diploid cells can "dedifferentiate" and reduce their synthesis of differentiated products (2, 3, 7). This loss of differentiated functions is also observed in cloned established cell lines where, if overgrowth is the cause, it is overgrowth by a dedifferentiated variant arising within the cloned population .The mechanisms by which cells lose the capacity to express differentiated functions and the nature of the differentiated program in nonexpressing variants are important issues for understanding the regulation and maintenance of cell differentiation. In the present study we have approached this problem by examining the regulation of muscle functions in heterokaryons and cell hybrids involving differentiation-defective myoblasts. We have previously shown that rat skeletal myosin light chain synthesis is induced when undifferentiated rat myoblasts are fused with polyethylene glycol to mononucleated differentiated chick skeletal myocytes (8,9). This suggests that differentiated chick myocytes contain factors...

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The Differentiated State of Normal and Malignant Cells or How to Define a “Normal” Cell in Culture

Cited by 197 publications

References 318 publications

Enrichment of breast cancer stem-like cells by growth on electrospun polycaprolactone-chitosan nanofiber scaffolds

Enrichment of breast cancer stem-like cells by growth on electrospun polycaprolactone-chitosan nanofiber scaffolds

AmotL2 disrupts apical–basal cell polarity and promotes tumour invasion

Control of differentiation in heterokaryons and hybrids involving differentiation-defective myoblast variants.

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