A hierarchy of ECM-mediated signalling regulates tissue-specific gene expression

Roskelley, Calvin D.; Srebrow, Anabella; Bissell, Mina J.

doi:10.1016/0955-0674(95)80117-0

Cited by 365 publications

(210 citation statements)

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“…Cell interaction with elements of the extracellular matrix impacts their adherence, motility, as well as protein and gene expression (for example, see Adams and Watt, 1993;Roskelly et al, 1995). In intact normal tissue epithelial cells bind to extracellular matrix molecules, which are organized into a complex multiprotein structure called the basement membrane.…”

Section: Introductionmentioning

confidence: 99%

A Cell Signal Pathway Involving Laminin-5, α3β1 Integrin, and Mitogen-activated Protein Kinase Can Regulate Epithelial Cell Proliferation

Gonzales¹,

Haan²,

Baker³

et al. 1999

MBoC

148

105

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Laminin-5 (LN5) is a matrix component of epithelial tissue basement membranes and plays an important role in the initiation and maintenance of epithelial cell anchorage to the underlying connective tissue. Here we show that two distinct LN5 function-inhibitory antibodies, both of which bind the globular domain of the ␣3 subunit, inhibit proliferation of epithelial cells. These same antibodies also induce a decrease in mitogenactivated protein kinase activity. Inhibition of proliferation by the function-perturbing LN5 antibodies is reversed upon removal of the antibodies and can be overcome by providing the antibody-treated cells with exogenous LN5 and rat tail collagen. Because epithelial cells use the integrin receptor ␣3␤1 to interact with both LN5 and rat tail collagen, we next investigated the possibility that integrin ␣3␤1 is involved in mediating the proliferative impact of LN5. Proliferation of human epithelial cells is significantly inhibited by a function-perturbing ␣3 integrin antibody. In addition, antibody activation of ␤1 integrin restores the proliferation of epithelial cells treated with LN5 functionperturbing antibodies. These data indicate that a complex comprising LN5 and ␣3␤1 integrin is multifunctional and contributes not only to epithelial cell adhesion but also to the regulation of cell growth via a signaling pathway involving mitogen-activated protein kinase. We discuss our study in light of recent evidence that LN5 expression is up-regulated at the leading tips of tumors, where it may play a role in tumor cell proliferation. INTRODUCTIONCell interaction with elements of the extracellular matrix impacts their adherence, motility, as well as protein and gene expression (for example, see Adams and Watt, 1993;Roskelly et al., 1995). In intact normal tissue epithelial cells bind to extracellular matrix molecules, which are organized into a complex multiprotein structure called the basement membrane. The major components of the latter include type IV collagen, proteoglycans, and laminins. One laminin isoform, laminin-5 (LN5), 1 in particular plays an important role in establishing firm adherence of epithelial cells to the basement membrane, because it is necessary for the assembly and maintenance of stable anchorage devices between epithelial cells and matrix called hemidesmosomes (Baker et al., 1996;Green and Jones, 1996). However, recent reports also indicate that LN5 is expressed at the budding tips of invading tumor cells, i.e., at sites where cancer cells are undergoing cell division but where there are most likely no hemidesmosomes (Pyke et al., 1994(Pyke et al., , 1995. This provides an indication § Corresponding author. E-mail address: j-jones3@nwu.edu. 1 Abbreviations used: BrdU, bromodeoxyuridine; DAPI, 4,6-diamidino-2-phenylindole; EGF, epidermal growth factor; FN, fibronectin; hLN5, human laminin-5; Ig, immunoglobulin; LN, laminin; MAP, mitogen-activated protein; MAPK, MAP kinase; RTC, rat tail collagen; rtLN5, rat laminin-5.© 1999 by The American Society for Cell Biology 259 that L...

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Section: Introductionmentioning

confidence: 99%

A Cell Signal Pathway Involving Laminin-5, α3β1 Integrin, and Mitogen-activated Protein Kinase Can Regulate Epithelial Cell Proliferation

Gonzales¹,

Haan²,

Baker³

et al. 1999

MBoC

148

105

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“…A hierarchy of milk protein gene expression based on hormonal, cell-cell, and cell-substratum interactions has been proposed to account for the differential regula-tion between ␤-casein and WAP gene expression (Bissell and Aggeler 1987;Roskelley et al 1995). Because C/ EBP␤ appears to be required for differentiation, and WAP is expressed later in the mammary gland differentiation program than ␤-casein, then either the C/EBP␤ −/− cells are sufficiently undifferentiated so as not to respond to these multiple signals required for WAP expression, or C/EBP␤ may indirectly influence the unique transacting factors required for WAP expression.…”

Section: Regulation Of Wap Expressionmentioning

confidence: 99%

C/EBPβ, but not C/EBPα, is essential for ductal morphogenesis, lobuloalveolar proliferation, and functional differentiation in the mouse mammary gland

Seagroves¹,

Krnacik²,

Raught³

et al. 1998

Genes Dev.

235

207

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The CCAAT/enhancer binding proteins (C/EBPs) are differentially expressed throughout mammary gland development and interact with binding sites within the promoter of a milk protein gene, ␤-casein. The specific roles of C/EBP␤ and C/EBP␣ in mouse mammary gland development and differentiation have been investigated in mice that carry targeted deletions of these genes. C/EBP␤ −/− virgin mice exhibited cystic, enlarged mammary ducts with decreased secondary branching. Transplantation of C/EBP␤ −/− mammary epithelium into the cleared mammary fat pads of nude mice confirmed that this defect in ductal morphogenesis was intrinsic to the epithelium. When treated with estrogen/progesterone (E+P) to simulate pregnancy, C/EBP␤ −/− mammary glands displayed only limited lobuloalveolar development and ductal side branching. Primary mammary epithelial cells obtained from E+P-treated C/EBP␤ −/− mice that were cultured on extracellular matrix gels did not functionally differentiate in response to lactogenic hormones despite their organization into three-dimensional structures. Expression of ␤-casein protein was inhibited 85%-100% and whey acidic protein (WAP) was undetectable. In contrast, no detectable alterations in mammary development or ␤-casein expression were observed in mammary outgrowths derived from newborn C/EBP␣ −/− mammary epithelium transplanted into the cleared mammary fat pads of syngeneic hosts. These results demonstrate that C/EBP␤, but not C/EBP␣, is required for ductal morphogenesis, lobuloalveolar development, and functional differentiation of mammary epithelial cells.

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“…In the usual monolayer cultures, cells undergo structural changes, nearly always accompanied by the loss of tissue-specific gene expression and by dedifferentiation (31). Cartilage cells, for instance, begin to transform into fibroblast-like cells after a few days on a plastic dish (32).…”

mentioning

confidence: 99%

Development of in vitro model systems for destructive joint diseases. Novel strategies for establishing inflammatory pannus

Schultz

Keyszer

Zacher

et al. 1997

Arthritis & Rheumatism

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Objective. To establish a novel 3-dimensional (3-D) in vitro model for the investigation of destructive processes in rheumatoid arthritis (RA).Methods. Two distinct culture systems were developed, consisting of RA synovial membrane and articular cartilage explants or interactive RA synovial cell/ chondrocyte cultures embedded in 3-D fibrin matrices. The expression of proteolytic enzymes, chondrocyte matrix architecture, and matrix degradation parameters was analyzed by immunohistochemistry.Results. Of 28 RA explant cultures, 16 displayed an invasion of synovial tissue into the cartilage explants, compared with 1 of 8 osteoarthritis explants. The expression of collagenase and vascular cell adhesion molecule l could be demonstrated at the cartilage-pannus junction. Of 20 interactive cell cultures, 18 revealed invasive behavior and remained vital for extended periods of time.Conclusion. The models presented allow us to study distinct aspects of destructive joint diseases under in vitro conditions that resemble human pathology. Moreover, our model is able to supplement animal experiments in basic research and drug testing.In rheumatoid arthritis (RA), the physiologic balance between matrix deposition and degradation is Supported by the Deutsche Forschungsgemeinschaft (grant Bu 44513-1 and 3-2) and the Hildegard Doerenkamp-Gerhard Zbinden Foundation.

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A hierarchy of ECM-mediated signalling regulates tissue-specific gene expression

Cited by 365 publications

References 118 publications

A Cell Signal Pathway Involving Laminin-5, α3β1 Integrin, and Mitogen-activated Protein Kinase Can Regulate Epithelial Cell Proliferation

A Cell Signal Pathway Involving Laminin-5, α3β1 Integrin, and Mitogen-activated Protein Kinase Can Regulate Epithelial Cell Proliferation

C/EBPβ, but not C/EBPα, is essential for ductal morphogenesis, lobuloalveolar proliferation, and functional differentiation in the mouse mammary gland

Development of in vitro model systems for destructive joint diseases. Novel strategies for establishing inflammatory pannus

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