Alterations in Integrin and Basement-Membrane Protein Expression by Malignant Breast Cells

Bergstraesser, Lynn M.; Weitzman, Sigmund A.

doi:10.3892/ijo.4.4.915

Cited by 4 publications

(5 citation statements)

References 0 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This suggests they have retained their characteristic luminal cell polarity or at least the ability to respond to an microenvironmentally or structurally generated orientation cue. Consistent with this observation, the few studies that have examined cell adhesion systems in these lesions have shown that they retain the full expression of, and a normal distribution for, all of the adherens junction and integrin molecules (Bergstraesser and Weitzman 1994;Gui et al 1995). Interestingly, when cultured in three-dimensional BM matrices, immortalized cells generated from these lesions are capable of growth arresting and recapitulating normal breast cytoarchitecture, implying that an altered in vivo breast microenvironment might be at least partially responsible for the expression of the proliferative phenotype (Petersen et al 1992;Howlett et al 1995;Weaver et al 1997).…”

Section: Changes In Cell Adhesion and Tissue Structure Are Associatedsupporting

confidence: 53%

“…Of the array of cell-ECM receptors known to exist in the breast, the best described and characterized are the integrin heterodimers. The luminal epithelial cells of the human breast express the laminin and (or) collagen integrin receptors: α1β1, α2β1, α3β1, αvβ1, α6β1 and α6β4, although the fibronectin receptor α5β1 has also been detected (Zutter et al 1990(Zutter et al ,1993Berdichevsky et al 1994;Bergstraesser and Weitzman 1994). Of these α2β1 and α3β1 have been shown to have a basolateral expression, while α6 and β4 are present where cells interact with the BM at the basal surface, and are thought to be localized to the hemidesmosomal junctions (Alford and Taylor-Papadimitriou 1996;Borradori and Sonnenberg 1996).…”

Section: Changes In Cell Adhesion and Tissue Structure Are Associatedmentioning

confidence: 99%

See 1 more Smart Citation

The importance of the microenvironment in breast cancer progression: recapitulation of mammary tumorigenesis using a unique human mammary epithelial cell model and a three-dimensional culture assay

Weaver

Fischer²,

Peterson³

et al. 1996

Biochem. Cell Biol.

200

175

View full text Add to dashboard Cite

The extracellular matrix (ECM) is a dominant regulator of tissue development and homeostasis. "Designer microenvironments" in culture and in vivo model systems have shown that the ECM regulates growth, differentiation, and apoptosis in murine and human mammary epithelial cells (MEC) through a hierarchy of transcriptional events involving the intricate interplay between soluble and physical signaling pathways. Furthermore, these studies have shown that these pathways direct and in turn are influenced by the tissue structure. Tissue structure is directed by the cooperative interactions of the cell-cell and cell-ECM pathways and can be modified by stromal factors. Not surprisingly then, loss of tissue structure and alterations in ECM components are associated with the appearance and dissemination of breast tumors, and malignancy is associated with perturbations in cell adhesion, changes in adhesion molecules, and a stromal reaction. Several lines of evidence now support the contention that the pathogenesis of breast cancer is determined (at least in part) by the dynamic interplay between the ductal epithelial cells, the microenvironment, and the tissue structure (acini). Thus, to understand the mechanisms involved in carcinogenesis, the role of the microenvironment (ECM as well as the stromal cells) with respect to tissue structure should be considered and studied. Towards this goal, we have established a unique human MEC model of tumorigenesis, which in concert with a three-dimensional assay, recapitulates many of the genetic and morphological changes observed in breast cancer in vivo. We are currently using this system to understand the role of the microenvironment and tissue structure in breast cancer progression.

show abstract

Section: Changes In Cell Adhesion and Tissue Structure Are Associatedsupporting

confidence: 53%

Section: Changes In Cell Adhesion and Tissue Structure Are Associatedmentioning

confidence: 99%

The importance of the microenvironment in breast cancer progression: recapitulation of mammary tumorigenesis using a unique human mammary epithelial cell model and a three-dimensional culture assay

Weaver

Fischer²,

Peterson³

et al. 1996

Biochem. Cell Biol.

200

175

View full text Add to dashboard Cite

show abstract

“…The reason for this dramatic difference in response to the ECM could lie in defects anywhere from the ECM to integrins to cytoskeleton to nuclear matrix and to the genes themselves (Bissell et al, 1982) and need not depend on the same genetic defects in different tumor cells. Our initial observations on the different behavior of "normal" and "malignant" human breast cancer cells inside EHS were confirmed by others (Shearer et al, 1992;Bergstraesser and Weitzman, 1993). Since, then, it has been observed that the morphogenic effect of EHS on normal and cancer cells makes the use of EHS a more sensitive assay than the soft agar assay for predicting whether cells are tumorigenic in nude mice (Basolo et al, 1996).…”

Section: A Basement Membrane (Ehs) Assaysupporting

confidence: 68%

“…The largest class of ECM receptors, the integrins, are now known to be the cellular antennas that sense the subtleties of the ECM and convert the chemistry of the microenvironment into subcellular signaling, which is then translated into form and function. Normal human breast epithelial cells express at least two β-integrins (β1 and β4) and four α-integrins (αl, α2, α3, α6) (Bergstraesser and Weitzman, 1994;Glukhova et al, 1995). The expression of integrins in breast cancer is usually altered quantitatively and/or qualitatively (Zutter et al, 1990;Mechtersheimer et al, 1993).…”

Section: Integrinsmentioning

confidence: 99%

Differentiation and Cancer in the Mammary Gland: Shedding Light on an Old Dichotomy

Petersen¹,

Rønnov‐Jessen

Weaver

et al. 1998

Advances in Cancer Research

View full text Add to dashboard Cite

In this brief review, the development of breast cancer is discussed from the vantage of phenotypic differentiation, similar to what has been considered over the years for leukemias and melanomas, both of which express easily visible differentiation markers (Hart and Easty, 1991;Clarke et al., 1995;Lynch, 1995;Sachs, 1996;Sledge, 1996). The review is divided into a theoretical background for human breast differentiation and a discussion of recent experimental results in our laboratories with differentiation of breast epithelial cells.In the theoretical background, in situ markers of differentiation of normal breast and carcinomas are discussed with emphasis on their possible implications for tumor therapy. So far, most of the emphasis regarding differentiation therapy of tumors has been focused on the possible action of soluble factors, such as colony-stimulating factors in leukemias and retinoic acids in solid tumors Sachs, 1996). However, an emerging and promising new avenue in this area appears to point to additional factors, such as the cellular form and extracellular matrix (ECM) (Bissell et al., 1982;Bissell and Barcellos-Hoff, 1987;Ingber, 1992). The recent interest in these parameters has evolved along with an increasing understanding of the molecular composition of the ECM, and of the molecular basis of the classical findings that normal cells-in contrast to tumor cellsare anchorage dependent for survival and growth (Folkman and Moscona, 1978;Hannigan et al., 1996). We now know that this is the case for epithelial as well as fibroblastic cells, and that interaction with ECM is crucial for such regulation. Indeed, ECM and integrins are emerging as the central regulators of differentiation, apoptosis, and cancer (Boudreau et al., 1995;Boudreau and Bissell, 1996;Werb et al., 1996;Weaver, et al., 1997).In the experimental part, we elaborate on our own recent experiments with functional culture models of the human breast, with particular emphasis on how "normal" and cancer cells could be defined within a reconstituted ECM. Special attention is given to integrins, the prominent ECM receptors. We further discuss a number of recent experimental results, all of which point to the same conclusion: namely that phenotypic reversion toward a more normal state for epithelial tumors is no longer an elusive goal. Thus "therapy by differentiation" could be broadened to include not only blood-borne tumors, but also solid tumors of epithelial origin.

show abstract

“…Alterations in basement membrane structure and composition during malignant transformation of breast epithelium as well as in carcinoma progression have been known for a long time. 19,20 As a new finding, we report on a strongly decreased or lacking deposition of the ␣3 and ␥2 chains of laminin-5 in the tumourstroma interface. Because laminin-5 is part of the anchoring filaments which connects hemidesmosomes of the cell to the basement membrane the strongly reduced laminin-5 deposition corresponds well with the ultrastructural observation of a reduced number of hemidesmosomes in breast cancer.…”

Section: Discussionmentioning

confidence: 59%

Loss of laminin‐5 in the epithelium–stroma interface: an immunohistochemical marker of malignancy in epithelial lesions of the breast

et al. 1999

View full text Add to dashboard Cite

As recently described, the malignant transformation of breast epithelium with expression of an invasive phenotype is associated with a decrease of hemidesmosomes. The reduced immunostaining of laminin-5 is in line with this finding because laminin-5 represents the major component of the anchoring filaments attaching hemidesmosomes to the basement membrane. We feel that immunohistochemical demonstration of laminin-5 may serve as a marker of benignity in epithelial breast lesions. While other carcinoma types exhibit an increased laminin-5 deposition, which has been suggested as an invasion promoting factor, the loss of laminin-5 in breast cancer supports the view that breast carcinomas do not utilize laminin-5 for invasion.

show abstract

Alterations in Integrin and Basement-Membrane Protein Expression by Malignant Breast Cells

Cited by 4 publications

References 0 publications

The importance of the microenvironment in breast cancer progression: recapitulation of mammary tumorigenesis using a unique human mammary epithelial cell model and a three-dimensional culture assay

The importance of the microenvironment in breast cancer progression: recapitulation of mammary tumorigenesis using a unique human mammary epithelial cell model and a three-dimensional culture assay

Differentiation and Cancer in the Mammary Gland: Shedding Light on an Old Dichotomy

Loss of laminin‐5 in the epithelium–stroma interface: an immunohistochemical marker of malignancy in epithelial lesions of the breast

Contact Info

Product

Resources

About